Article

Estrus- and steroid-induced changes in circadian rhythms in a diurnal rodent, Octodon degus

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Abstract

Diurnal Octodon degus exhibited marked alterations in activity and temperature in conjunction with the 3 wk estrous cycle when housed in LD12:12 light cycle. On the day of estrus, mean daily activity increases 109%, mean core temperature rises .4 degree C, activity onset is advanced 2 h, and amplitudes of both rhythms decline compared with the 3 days prior to estrus. On the day following estrus, activity onset was delayed 4.9 h, and mean activity and core temperature fell below that of the preestrus period. Ovariectomy significantly reduced mean temperature (.98 degree C) but did not significantly alter mean activity, and eliminated cyclic effects of estrus. Estrogen replacement led to a nonsignificant elevation in mean activity and core temperature with no change in the phase angle of entrainment. Progesterone replacement significantly reduced mean core temperature and mean activity, while only the phase angle difference between temperature minimum and activity onset was significantly altered. Intact degus maintained in constant darkness displayed only transient fluctuations in activity onset and temperature minimum during and after estrus. Estrogen or progesterone treatment of ovariectomized, free-running degus altered mean temperature and activity levels, but did not influence tau. Changes in phase angle of entrainment during estrus are not the result of hormone effects on the circadian clock but likely reflect increased or decreased levels of activity.

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... Rats also exhibit higher levels of activity levels on estrus along with advanced phase angle of entrainment, increased activity duration, and a more consolidated active phase [6,163]. Likewise, female degus display increased activity levels and a 5 h advance of activity onset on the day of estrus [84]. Estrus can modulate daily rhythms in mice (Fig. 3B), but reports of estrus effects are more varied in this species, with increased activity on proestrus [77,126], overall more activity in females than males [17], or no difference by sex or estrous phase [82,122]. ...
... Subsequent work suggests that the effect of castration and exogenous androgens on period in mice is dependent on dim red light exposure during free-running conditions [22]. Lastly, gonadectomy and exogenous hormone exposure does not alter period in adult male or female degus [70,84,87], indicating that the sex difference in period does not require activational effects of gonadal hormones in this species. ...
... Estrogen signaling also modulates activity levels in male and female mice through multiple mechanisms involving both ERS1 and ERS2 [17,18,122]. Lastly, progesterone administration decreases activity levels in hamsters and degus [84,149], complementing its antagonistic effects on circadian period. In addition to modulating activity levels over the estrus cycle, this action of progesterone may also serve to suppress activity levels during pregnancy and lactation. ...
Article
The circadian system regulates behavior and physiology in many ways important for health. Circadian rhythms are expressed by nearly every cell in the body, and this large system is coordinated by a central clock in the suprachiasmatic nucleus (SCN). Sex differences in daily rhythms are evident in humans and understanding how circadian function is modulated by biological sex is an important goal. This review highlights work examining effects of sex and gonadal hormones on daily rhythms, with a focus on behavior and SCN circuitry in animal models commonly used in pre-clinical studies. Many questions remain in this area of the field, which would benefit from further work investigating this topic.
... During the human menstrual cycle circadian rhythms may also shift their phasing, but results are contradictory [109,143,144,167]. Indeed, in adult laboratory rodents a wide variety of gonadal hormones can affect the phase of circadian rhythms, including estrogens, progestins, androgens, and non-traditional neuroactive steroids (e.g., rats: [8,17], hamsters: [49,51,129], mice: [23,47,78,90], degus: [80,100]). ...
... Gonadal hormones can influence other circadian parameters as well, including endogenous period [7,23,47,49,91,129,212], rhythm amplitude [8,17,100], range of entrainment [49], zeitgeber sensitivity [23,51,79,81], and oscillator coupling [126,128,187]. Many of these parameters also exhibit sex differences. ...
... For example, castrated adult male rodents under entrained and free-running conditions had activity that was more dispersed across the active period [128], such that activity at the beginning of their active period in the early night was less cohesive, diminished, lost, or delayed [47,49,78,90,128, although see 23 and 80]. This was also true of ovariectomized adult female rodents: they lost the phase advance and increase in wheel running activity that typically accompanies estrus [49,78,100,129], and in general exhibited a more dispersed activity distribution and delayed activity rhythm phase [187, 203, although see 23]. ...
... In hamsters, estrogens positively influence the amplitude of locomotion [13][14][15][16]. The circadian period shortens during the estrus or proestrus phase [17][18][19]. In ovariectomized hamsters, an implant that chronically releases of estradiol shortens the free running period, but this effect is blocked by the administration of progesterone [13]. ...
... In rats, ovariectomy (OVX) increases food intake, body weight, and decreases activity and sexual behavior [20,21]; it also lengthens the period of free-running rhythms of locomotion [17]. In mice C57BL/6 J, OVX reduces the activity [22] and in degu Octodon degus, no effect on activity was noted [19]. ...
... The estrous cycle involves the release of ovarian hormones that may influence circadian organization in both hamsters and rats associated with changes in τ, amplitude and ψ [13,17,48]; such variation has been defined as "scalloping" [15]. Changes in τ and ψ have also been described during proestrus when the highest concentration of estradiol was present [16,19,29,49]. In the present study, a scalloping was noted in the daily average amplitude of locomotor activity of intact N. alstoni along the estrous cycle every 4.5-6.5 days, associated with less stability in its acrophase (Fig. 3A) and a positive ψ. ...
Article
Recently, the relationship between the circadian system and female reproduction has been of great interest; ovarian hormones can modify the amount and distribution of daily activity differently in rodent species. The volcano mouse Neotomodon alstoni is a species in which it is possible to study the circadian rhythm of locomotion, and it offers comparative information about the influence of ovaries on the circadian system. In this study, we used infrared crossings to compare free movement in intact and sham-operated or ovariectomized mice. We analyzed behavioral and endocrine changes related to the estrous cycle and locomotor circadian rhythm in free-running mice and photic phase shifting. Evidence shows that intact mice present a scalloped pattern of daily activity during the estrous cycle. In constant darkness, the ovariectomy reduces the total amount of activity, shortens the free-running circadian period of locomotion and increases photic phase shifts during the early subjective night. During entrainment, the ovariectomized mice increased the amplitude of total activity during the scotophase, and delay the time of activity onset. These results suggest that ovarian hormones in N. alstoni modulate the circadian rhythm of locomotor activity in a species-specific manner.
... (Reynolds and Wright, 1979). The vaginal membrane is open only during proestrus and estrus (Labyak and Lee, 1995). The uterus is bicornuate (Woods and Boraker, 1975). ...
... Earlier literature suggested that degus were induced ovulators and required the presence of a male for cycles to occur (Weir 1970(Weir , 1974. However, vaginal patency, increased wheel running activity, increased body temperature, and sexual receptivity (estrus) all occur in the same 1-2-day period and occur in a cyclical and regular basis (Labyak and Lee, 1995). The average cycle length in adult females is 21.1  0.56 days and can range from 16-26 days (Labyak and Lee 1995;Mahoney et al., 2005). ...
... However, vaginal patency, increased wheel running activity, increased body temperature, and sexual receptivity (estrus) all occur in the same 1-2-day period and occur in a cyclical and regular basis (Labyak and Lee, 1995). The average cycle length in adult females is 21.1  0.56 days and can range from 16-26 days (Labyak and Lee 1995;Mahoney et al., 2005). Cycle length is uniform within an individual and thus one can reliably predict when the next day of estrus will occur using physiological information. ...
Chapter
This chapter studies the degu, its attributes, and uses as a laboratory animal species. Degus are mostly associated with the study of circadian rhythms due to their diurnal activities in the wild and they have also been established as valuable animal models in the study of a wide range of scientific areas including developmental biology, diabetes mellitus, cataracts, and Alzheimer's disease. The organ systems and physiological processes that have made the degu a useful animal model in various areas of research have been described in detail such as external features, circulatory system, and the nervous system. Due to less established laboratory colonies, much remains to be discovered regarding optimal housing, disease control, and veterinary care of the species. The chapter describes the management, husbandry, nutrition, diseases, and behavioral patterns of the degu. The degu is chosen as an animal for experimental model due to its characteristics such as complex familial and social structure and highly developed vocal repertoire. Also degus are relatively long-lived when compared to many other laboratory rodents. The research models that have been explained are thymic research, Alzheimer's disease, production of antisera, and atherosclerosis.
... Specifically, gonadally intact female rats, hamsters, and degus have the greatest level of activity during proestrus and estrus, when circulating estrogen levels are highest (Morin et al., 1977b;Wollnik & Turek, 1988;Mahoney et al., 2011). Further, in these species the period of the endogenous free-running rhythm (tau) in constant conditions is shortest during estrus (Fitzgerald & Zucker, 1976;Albers et al., 1981;Labyak & Lee, 1995). ...
... Ovariectomy of female rodents causes a decrease of daily wheel-running activity and a lengthening of tau, and estradiol replacement increases activity levels and shortens tau (Gentry & Wade, 1976;Morin et al., 1977b;Albers, 1981;Labyak & Lee, 1995). ...
... The phase angle of activity onset has been characterized in different species across the estrous cycle and is typically advanced on days of high circulating estrogens (Fitzgerald & Zucker, 1976;Morin et al., 1977a;Albers et al., 1981;Wollnik & Turek, 1988;Labyak & Lee, 1995). In the current study, all animals regardless of genotype, had a phase advance in the timing of their activity in response to estradiol. ...
Article
Full-text available
Estradiol influences the level and distribution of daily activity, the duration of the free-running period, and the behavioral phase response to light pulses. However, the mechanisms by which estradiol regulates daily and circadian rhythms are not fully understood. We tested the hypothesis that estrogens modulate daily activity patterns via both classical and "non-classical" actions at the estrogen receptor subtype 1 (ESR1). We used female transgenic mice with mutations in their estrogen response pathways; ESR1 knock-out (ERKO) mice and "non-classical" estrogen receptor knock-in (NERKI) mice. NERKI mice have an ESR1 receptor with a mutation in the estrogen-response-element binding domain, allowing only actions via "non-classical" genomic and second messenger pathways. Ovariectomized female NERKI, ERKO, and wildtype (WT) mice were given a subcutaneous capsule with low- or high-dose estradiol and compared with counterparts with no hormone replacement. We measured wheel-running activity in a light:dark cycle and constant darkness, and the behavioral phase response to light pulses given at different points during the subjective day and night. Estradiol increased average daily wheel-running, consolidated activity to the dark phase, and shortened the endogenous period in WT, but not NERKI and ERKO mice. The timing of activity onset during entrainment was advanced in all estradiol-treated animals regardless of genotype suggesting an ESR1-independent mechanism. We propose that estradiol modifies period, activity level, and distribution of activity via classical actions of ESR1 whereas an ESR1 independent mechanism regulates the phase of rhythms.
... Both male and female C57 mice in our experiment had comparable FRPs in line with previous findings that found no period difference between C57 male and female mice (Kuljis et al., 2013). Sex differences have been previously reported in other species such as the golden hamster (Davis et al., 1983;Schull et al., 1989) and Octodon degus (Labyak and Lee, 1995;Lee and Labyak, 1997); however, the male animals in these studies showed longer FRPs than females. Sex differences may be due to differences in gonadal steroids, which can influence circadian period (Morin et al., 1977;Albers, 1981;Karatsoreos et al., 2007;Royston et al., 2014). ...
... Some manipulations of estrogen can alter rhythm properties. In hamsters, chronic estradiol exposure shortens FRP (Morin et al., 1977), while ovariectomy lengthens FRP in rats, hamsters, and O. degus (Morin et al., 1977;Albers, 1981;Labyak and Lee, 1995). However, ovariectomy has no effect on the freerunning period in mice (Iwahana et al., 2008). ...
Article
Full-text available
Animals with altered freerunning periods are valuable in understanding properties of the circadian clock. Understanding the relationship between endogenous clock properties, entrainment, and influence of light in terms of parametric and non-parametric models can help us better understand how different populations adapt to external light cycles. Many clinical populations often show significant changes in circadian properties that in turn cause sleep and circadian problems, possibly exacerbating their underlying clinical condition. BTBR T+Itpr3tf/J (BTBR) mice are a model commonly used for the study of autism spectrum disorders (ASD). Adults and adolescents with ASD frequently exhibit profound sleep and circadian disruptions, including increased latency to sleep, insomnia, advanced and delayed sleep phase disorders, and sleep fragmentation. Here, we investigated the circadian phenotype of BTBR mice in freerunning and light-entrained conditions and found that this strain of mice showed noticeably short freerunning periods (~22.75 h). In addition, when compared to C57BL/6J controls, BTBR mice also showed higher levels of activity even though this activity was compressed into a shorter active phase. Phase delays, and phase advances to light were significantly larger in BTBR mice. Despite the short freerunning period, BTBR mice exhibited normal entrainment in light-dark cycles and accelerated entrainment to both advanced and delayed light cycles. Their ability to entrain to skeleton photoperiods of 1 min suggests that this entrainment cannot be attributed to masking. Period differences were also correlated with differences in the number of vasoactive intestinal polypeptide-expressing cells in the suprachiasmatic nucleus (SCN). Overall, the BTBR model, with their unique freerunning and entrainment properties, makes an interesting model to understand the underlying circadian clock.
... Estrogens also can affect circadian properties in rodents (Blattner and Mahoney, 2015). For example, natural increases in estrogen concentrations during estrous as well as experimental estrogen administration phase-advances behavioural activity rhythms in some rodent species (Albers et al., 1981;Labyak and Lee, 1995;Morin et al., 1977). Estrogens can also increase overall behavioural locomotor activity, and estrogens may also modulate the effectiveness of nonphotic stimuli mediated through e.g. ...
... wheel-running on circadian rhythms (Legan et al., 2015). However, the proximate mechanism underlying these estrogenic actions in female rodents are still debated, and may involve changes in activity levels, arousal, sleep and responsiveness to nonphotic stimuli rather than changes in τ-although species-differences may also account for some divergences in mechanisms (Labyak and Lee, 1995;Mong et al., 2011;Yan and Silver, 2016). ...
Thesis
Full-text available
Adaptive flexibility of mammalian circadian organisation Sjaak J Riede
... Oestrogens also can affect circadian properties in rodents [127]. For example, natural increases in oestrogen concentrations during oestrous as well as experimental oestrogen administration phaseadvances behavioural activity rhythms in some rodent species [128][129][130]. Oestrogens can also increase overall behavioural locomotor activity, and oestrogens may also modulate the effectiveness of non-photic stimuli mediated through, for example, wheel-running on circadian rhythms [131]. ...
... Oestrogens can also increase overall behavioural locomotor activity, and oestrogens may also modulate the effectiveness of non-photic stimuli mediated through, for example, wheel-running on circadian rhythms [131]. However, the proximate mechanism underlying these oestrogenic actions in female rodents is still debated and may involve changes in activity levels, arousal, sleep and responsiveness to non-photic stimuli rather than changes in t, although species differences may also account for some divergences in mechanisms [48,130,132]. ...
Article
Under natural conditions, many aspects of the abiotic and biotic environment vary with time of day, season or even era, while these conditions are typically kept constant in laboratory settings. The timing information contained within the environment serves as critical timing cues for the internal biological timing system, but how this system drives daily rhythms in behaviour and physiology may also depend on the internal state of the animal. The disparity between timing of these cues in natural and laboratory conditions can result in substantial differences in the scheduling of behaviour and physiology under these conditions. In nature, temporal coordination of biological processes is critical to maximize fitness because they optimize the balance between reproduction, foraging and predation risk. Here we focus on the role of peripheral circadian clocks, and the rhythms that they drive, in enabling adaptive phenotypes. We discuss how reproduction, endocrine activity and metabolism interact with peripheral clocks, and outline the complex phenotypes arising from changes in this system. We conclude that peripheral timing is critical to adaptive plasticity of circadian organization in the field, and that we must abandon standard laboratory conditions to understand the mechanisms that underlie this plasticity which maximizes fitness under natural conditions. This article is part of the themed issue ‘Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals’.
... Animal studies provide strong evidence that the exposure to steroid hormones during the development and circulating steroid hormones in adults results in sex differences in the expression of biological rhythms, including sleep-wake patterns. In female rodents, total daily wheel-running activity depends on the stage of the reproductive cycle; when estrogens are elevated, there is an increase in both total wheel-running activity and phase advance in the timing of the daily activity onset in hamsters (Morin et al. 1977), degus (Labyak & Lee 1995) and rats (Wollnik & Turek 1988). In rats, the duration of the active period (α) in constant conditions and in a light:dark (LD) cycle varies throughout the estrous cycle with the greatest duration of the active period occurring on the day of estrus . ...
... Intact and estradiol-treated ovariectomized female mice have a longer duration of wake time than males (Paul et al., 2006(Paul et al., , 2009. Ovariectomy lengthens free-running period (τ ) and estradiol replacement shortens free-running period in female rats (Albers 1981), hamsters (Morin et al. 1977) and degus (Labyak & Lee 1995). There are species differences in the expression of circadian rhythms, for example, in the phase response to light pulse (Daan & Pittendrigh 1976), it is equally possible that the effects of steroid hormones on the expression of circadian rhythms are also dependent upon species. ...
Article
There are sex differences in free-running rhythms, activity level and activity distribution that are attributed, in part, to the action of gonadal hormones. We tested the hypothesis that non-classical estrogenic signaling pathways at estrogen receptor subtype 1 (ESR1) modify the amplitude and phase of activity. We used ESR1 knock-out mice (ERKO) and non-classical estrogen receptor knock-in mice (NERKI). ERKO animals are unable to respond to estrogen at the ESR1 and NERKI animals lack the ability to respond to estrogens via the estrogen response element-mediated pathway, but can still respond via non-classical mechanisms. We compared intact male and female ERKO, NERKI and wildtype (WT) mice with respect to total wheel-running activity, activity distribution across the 24-h day, phase angle of activity onset and free-running period (τ) and the duration of activity in constant conditions. WT females had significantly greater activity than WT males, and this activity was more consolidated to the dark phase of the light:dark cycle. These sex differences were absent in the NERKI and ERKO animals. Among females, NERKI and ERKO animals had greater activity during the light phase than WT counterparts. Additionally, we have identified a novel contribution of non-classical estrogen signaling pathways on the distribution of activity. Our data suggest that total activity is ESR1-dependent and daily activity patterns depend on both classical and non-classical actions of estrogens. These data will aid in identifying the mechanisms underlying sex differences in sleep-wake cycles and the influence of steroid hormones on circadian patterns.
... Similar to humans, degus also show changes in their activity patterns around the time of puberty (Hagenauer et al., 2011). This has inspired studies examining the organizational and activational effects of sex steroid hormones on circadian rhythms in a diurnal rodent system (Hagenauer et al., 2011;Hummer et al., 2007;Jechura et al., 2006aJechura et al., ,b, 2003Jechura et al., , 2000Jechura and Lee, 2004;Labyak and Lee, 1995). As degus are highly social, they have also been used as a model to examine the relative importance of social cues on activity patterns (Jechura et al., 2006a(Jechura et al., ,b, 2003Jechura and Lee, 2004). ...
... Compared to males, adult female degus have a free-running circadian rhythm that is 30 min longer (Labyak and Lee, 1995). This sex difference is likely due to organizational effects of sex steroid hormones during the pre-pubertal stage, as degus gonadectomized before puberty show no sex difference in free-running circadian rhythm (Hummer et al., 2007). ...
Article
The Common Degu (Octodon degus) is a small rodent endemic to central Chile. It has become an important model for comparative vertebrate endocrinology because of several uncommon life-history features - it is diurnal, shows a high degree of sociality, practices plural breeding with multiple females sharing natal burrows, practices communal parental care, and can easily be studied in the laboratory and the field. Many studies have exploited these features to make contributions to comparative endocrinology. This review summarizes contributions in four major areas. First are studies on degu stress responses, focusing on seasonal changes in glucocorticoid (GC) release, impacts of parental care on offspring GC responses, and fitness consequences of individual variations of GC responses. These studies have helped confirm the ecological relevance of stress responses. Second are studies exploring diurnal circadian rhythms of melatonin and sex steroids. These studies have formed important work translating circadian biology from nocturnal laboratory rodents to diurnal humans. Third are studies that exploit the open nature of degu natural habitat, combined with laboratory studies, to explore the impact of testosterone on agonistic behavior. Studies have focused primarily on male:male, female:female, male:female, and parental behaviors. Fourth, are contributions to the study of female masculinization from male siblings in the uterus. These studies have focused on both the behavioral consequences of masculinization and the impact of those behaviors on fitness. Taken together, the studies reviewed here have formed a strong foundation for further studies in the degu so that future studies can address how endocrinological components underlie new mechanistic connections to the ecological effects on behavior and fitness.
... In contrast, Freedman et al. found that the plasma level of estradiol was not different between postmenopausal women with and without hot flushes (Freedman et al., 1995), suggesting a lesser involvement of circulating estrogen in this condition. In another study, estrogen administration was found to have no influence on the circadian T b rhythm in female rodents (Labyak and Lee 1995). Consequently, it remains unclear if estrogen has an influence on thermoregulatory responses. ...
Book
Autonomic and behavioral thermoregulation is essential for humans and animals to survive in hot and cold environments. Peri- and post-menopausal women may suffer from hot flushes, i.e., the sudden onset of face flushing, sweating, and heat, disturbances in circadian body temperature changes, and a chilly feeling, which is called “hie-sho” in Japan. A decrease and fluctuation in the plasma concentration of the female sex hormones, estrogen and progesterone, appear to be involved in these failures of thermoregulation in women. While progesterone has an established pyrogenic effect, the role of estrogen in autonomic and behavioral thermoregulation remains unknown. This monograph discusses the effect of estrogen on autonomic and behavioral thermoregulation in female rats with the help of data tables and figures from our study and previous studies by other researchers. The circulating level of estrogen during the estrus cycle in normal female rats maintains body temperature in the cold via the hypothalamus and non-shivering thermogenesis in the interscapular brown adipose tissue. Local administration of estrogen to the medial preoptic areas in the hypothalamus in ovariectomized rats influences body temperature by suppressing heat dissipation from the body surface in cold environments. The role of estrogen in autonomic thermoregulation in the cold is to maintain body temperature by causing non-shivering thermogenesis and heat dissipation. On the other hand, systemic estrogen in ovariectomized rats increases the duration of tail-hiding behavior in the mild cold. In a previous study, we showed that this behavior was a new indicator for assessing behavioral thermoregulation in a cold environment. This indicates that the role of estrogen in behavioral thermoregulation in cold temperatures may be to enhance behavioral thermoregulation. However, the mechanism of why and how estrogen influences tail-hiding behavior only in mildly cold temperatures remains unknown and needs to be clarified in future studies. Key Words: estrogen, body temperature, thermoregulatory behavior, tail temperature, hypothalamus [Acknowledgements] This book would not have been possible if I did not receive valuable comments from the reviewers of the Publishing Committee in Waseda University. Additionally, I thank Dr. Kei Nagashima, my advisor for the master and doctoral courses of study at Waseda University as well as for his helpful direction and technical support throughout the research. I am grateful to Dr. Ken Tokizawa, Ms. Madoka Tohi, Ms. Shuri Marui, Dr. Mayumi Nakamura-Matsuda, Dr. Kazuyuki Kanosue, Dr. Korehito Yamanouchi, Dr. Kazuhiko Imaizumi, Mr. Takashi Uchida and the other laboratory members in Waseda University for their valuable comments. I also thank Dr. Yoji Osako, Dr. Naoko Yamaguchi and Dr. Kazunari Yuri in Kochi Medical School for their support. This study was supported partly by the Ministry of Education, Science, Sports, and Culture; Grant-in-Aids for Scientific Research (B), Nos. 17052023 and 17390062; Grant-in-Aid for Young Scientists, No. 24800047; the Ibuka Fund from Waseda University, Grant for Young Scientists from Kochi Medical School and Hayashi Memorial Foundation for Female Natural Scientists. Finally, I really thank Dr. Larry I. Crawshaw for his helpful advice and manuscript reading.
... This is consistent with the findings that in mice lacking ERa, the free-running period in constant dark is not different from wild type controls in both males and females [59]. However, in other rodent species, ovariectomy can lead to a lengthening of the free-running period, pointing to a species difference in estrogenic regulation of circadian rhythms [60][61][62]. ...
... While sex differences have been described in various circadian parameters, they are most often found to be highly species specific. Differences between the sexes are modest in regard to certain parameters, such as the endogenous periodicity of the internal rhythm (Davis et al. 1983;Labyak and Lee 1995;Lee and Labyak 1997;Schull et al. 1989). These differences are more pronounced in other parameters, such as daily activity onset, and responses to photic and nonphotic cues and their influence on circadian behavior. ...
Article
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Sex differences in alcohol use and abuse are pervasive and carry important implications for the prevention and treatment of alcohol use disorder (AUD), yet insight into underlying sexually dimorphic mechanisms is limited. Growing experimental and clinical evidence points to an important influence of circadian rhythms and circadian clock genes in the control of alcohol drinking behavior and AUD. Sex differences in the expression of circadian rhythms and in the molecular circadian clock that drive these rhythms have been reported in humans and animals. While studying the role of striatal circadian clock gene expression in the control of affective and goal-directed behaviors, we uncovered a novel sexually dimorphic function of the clock genes Bmal1 and Per2 in the control of voluntary alcohol consumption in mice, which may contribute to sex differences in alcohol drinking behavior. In this mini review, we briefly discuss relevant literature on AUD, circadian rhythms and clock genes, and on sex differences in these domains, and describe our own findings on clock genes as sexually dimorphic regulators of alcohol drinking behavior in mice.
... Sex differences in period are highly species-specific, but even when present the differences are generally modest. Free-running period in rats and golden hamsters is longer in males than females (4,5); however, the differences in period are very small, whereas in Octodon degus period is longer in females by approximately half an hour (6,7). In mice with a C57BL/6J background, there does not appear to be a sex difference in free-running period (3). ...
Article
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There is a strong bias in basic research on circadian rhythms toward the use of only male animals in studies. Furthermore, of the studies that use female subjects, many use only females and do not compare results between males and females. This review focuses on behavioral aspects of circadian rhythms that differ between the sexes. Differences exist in the timing of daily onset of activity, responses to both photic and non-photic stimuli, and in changes across the lifespan. These differences may reflect biologically important traits that are ecologically relevant and impact on a variety of responses to behavioral and physiological challenges. Overall, more work needs to be done to investigate differences between males and females as well as differences that are the result of hormonal changes across the lifespan.
... The phase angle of activity onset relative to the time of lights-off is advanced in intact female rats on the day of estrus when serum estradiol levels peak and progesterone levels are at their minimum (17,53). It is similarly advanced in female hamsters administered estradiol (27) but is unaffected in female Octodon degus treated with progesterone (19). Although these data support the hypothesis that increased estrogenic signaling strengthens entrainment to light (31), they do not rule out the possibility that changes in progesterone signaling may also modulate the phase angle of activity onset. ...
Article
Estrogenic signaling shapes and modifies daily and circadian rhythms, the disruption of which have been implicated in psychiatric, neurologic, cardiovascular, and metabolic disease, among others. However, the activational mechanisms contributing to these effects remain poorly characterized. To determine the activational impact of estrogen on daily behavior patterns and differentiate between the contributions of the estrogen receptors ESR1 and ESR2, ovariectomized adult female mice were administered estradiol, the ESR1 agonist propylpyrazole triol (PPT), the ESR2 agonist diarylpropionitrile (DPN), or cholesterol (CTL). Animals were singly housed with running wheels in a 12:12 Light:Dark cycle or total darkness. Estradiol increased total activity and amplitude, consolidated activity to the dark phase, delayed the time of peak activity (acrophase of wheel running), advanced the time of activity onset, and shortened the free running period (τ), but did not alter the duration of activity (α). Importantly, activation of ESR1 or ESR2 differentially impacted daily and circadian rhythms. ESR1 stimulation increased total wheel running and amplitude, and reduced the proportion of activity in the light vs the dark. Conversely, ESR2 activation modified the distribution of activity across the day, delayed acrophase of wheel running, and advanced the time of activity onset. Interestingly, τ was shortened by estradiol or either estrogen receptor agonist. Finally, estradiol-treated animals administered a light pulse in the early subjective night, but no other time, had an attenuated response compared to CTL. This decreased phase response was mirrored by animals treated with DPN, but not PPT. To conclude, estradiol has strong activational effects on the temporal patterning and expression of daily and circadian behavior, and these effects are due to distinct mechanisms elicited by ESR1 and ESR2 activation.
... Por otra parte, no debe olvidarse el estudio de la influencia que tienen las hormonas ováricas sobre el NSQ, pues los resultados de algunos experimentos con roedores ovariectomizados afectan respuestas circadianas (Morin, Fitzgerald y Zucker, 1977;Morin y Cumming, 1982;Labyak y Lee, 1995;Iwahana et al., 2008;Blattner y Mahoney, 2012;Royston et al., 2014). ...
Article
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Resumen Para garantizar el éxito reproductivo, los mamíferos requieren de la organización de muchos procesos fisiológicos y conductuales, así como la participación de señales del medio ambiente. Durante la reproducción, las hembras secretan diversas hormonas que inducen de manera óptima la ovulación para la posible fertilización. Dichos eventos, se presentan rítmicamente y están vinculados a un proceso circadiano de regulación. El núcleo supraquiasmático (NSQ) del hipotálamo es considerado el reloj maestro de los ritmos circadianos en mamí-feros e influye diariamente, vía neural y endocrina en diversos sistemas fisiológicos. La fisiología reproductiva es coor-dinada por las conexiones del NSQ con otros núcleos hipotalámicos encargados de la liberación de las hormonas del eje hipotálamo-hipófisis-gónadas (HHG). En esta revisión se abordará la comunicación entre los sistemas circadiano y el eje HHG para la regulación del ciclo estral, con particular énfasis en el reciente descubrimiento del ovario como oscilador circadiano periférico en roedores. Palabras clave: ovario, sistema circadiano, oscilador periférico, fisiología reproductiva. Abstract To secure reproductive success, mammals require the establishment of several physiological and behavioral processes, as well as the involvement of environmental signals. During reproduction, females secrete a number of different hormones to induce an optimal ovulation for a potential fertilization. These events are presented rhythmically and are linked to the circadian regulation. The suprachiasmatic nucleus (SCN) in the hypothalamus is considered the master clock of circadian rhythms in mammals, it affects neural and endocrine manner on several physiological systems daily. Reproductive physiology is coordinated by SCN connections with other hypothalamic areas, which are responsible for the release of the hormones involved in the hypothalamic-pituitary-gonads axis (HPG). This review will address the communication between the circadian system and the HPG axis in the regulation of the estrous cycle, with a particular emphasis on the recent discovery of the role of the ovary as a peripheral circadian osci-llator in rodents.
... However, one can notice that in these species there is a consis-tent elevation of body temperature throughout the day and a fall during the night. Daily rhythmicity of body temperature has been extensively documented in laboratory rats (4,41,45,58,61,105,112,138,139,155,168,170,191,209,210,227,228,234,263,266,278,297,324,332,337,348,357,360,388,418,423,427,442,469,478,488,490,497,499,514,521,536,544,547,564,589,591,592), as well as in domestic mice (42,85,86,137,232,256,274,294,366,487,504,538,571,572), golden hamsters (56, 59, 76, 84, 111, 141, 166, 424, 426, 568), and many other rodent species (7,48,130,152,163,165,184,190,198,252,253,280,284,289,302,317,356,425,428,429,431,432,470,472,473,519,570). A large number of studies have also been conducted on primates (27,145,148,154,205,345,389,390,509,528,535,539,582), including humans (16,17,32,38,64,66,80,95,104,118,129,149,172,211,212,265,276,277,288,292,295,300,312,325,349,358,361,370,406,479,491,495,513,515,520,551,555,559,573,576), as well as in dogs (197,417,448), cats (246,282,412), goats (28,238,239,395), sheep (50, 305,339,340,393,419), cattle (13,182,183,293,396), other mammals (30,49,77,88,142,153,194,204,230,233,248,268,308,316,391,394,397,443,457,466,560,574), and many species of birds (20,44,52,144,173,249,250,331,375,376,413,414,553,580,581,588,594). ...
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Animals, plants, and microorganisms exhibit numerous biological rhythms that are generated by numerous biological clocks. This article summarizes experimental data pertinent to the often-ignored issue of integration of multiple rhythms. Five contexts of integration are discussed: (i) integration of circadian rhythms of multiple processes within an individual organism, (ii) integration of biological rhythms operating in different time scales (such as tidal, daily, and seasonal), (iii) integration of rhythms across multiple species, (iv) integration of rhythms of different members of a species, and (v) integration of rhythmicity and physiological homeostasis. Understanding of these multiple rhythmic interactions is an important first step in the eventual thorough understanding of how organisms arrange their vital functions temporally within and without their bodies. © 2012 American Physiological Society. Compr Physiol 2:1213-1239, 2012.
... Keep one male with one or two females and their litters (Ebensperger et al. 2007). Monitor their reproductive maturation by observing the timing of vaginal opening in females and penile development in males (see Fig. 1; Labyak and Lee 1995). ...
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The Octodon degu is a native rodent species from South America, which lives in colonies with a well-structured social organization grouping of 5-10 young and 2-5 adult animals sharing a burrow system. They show a temperature-dependent diurnal-crepuscular activity pattern. In nature they rarely survive 2 yr, mostly because of predation. However, in captivity, females reproduce for 4-4.5 yr, and both sexes live for 5-7 yr. Males remain fertile until death. Some care is required to maintain healthy degus, particularly breeding females. Here we describe husbandry and breeding guidelines from the experience of the University of Michigan degu colony. With the husbandry practices described here, 90% of pups born in our colony reach maturity (6 mo of age), and no diarrheal diseases are apparent in our adult population.
... Paradoxically, in arctic ground squirrels, androgens do not decrease in response to onset of winter, and this is believed to promote anabolism of muscle in preparation for catabolism during the long hibernation season [5] . In female rodents the effects of steroid sex hormones on thermal physiology are mixed, with either oestradiol or progesterone administration affecting thermoregulatory activities in some species , and having no effect in others [29,11,44,42,57]. Alongside this are pronounced changes in body condition indicators promoted by the sex hormones [30,31] . ...
Article
Seasonal cycles of reproduction are common in many mammals and these are combined with the necessary energy budgeting for thermoregulatory challenges. Many mammals meet the challenge of changing environmental temperatures in winter by using torpor, a controlled reduction in body temperature and metabolic rate. We aimed to determine the effects of photoperiod and reproductive hormones on the seasonal cycles of reproduction and torpor use in a marsupial that commences reproduction in winter, the stripe-faced dunnart, Sminthopsis macroura. Males and females were placed under LD 14:10 and natural reproductive hormones blocked by either flutamide (males) or mifepristone (females) or tamoxifen (females). Reproductive parameters, metabolic rate and torpor variables were determined. The same animals were then placed under LD 10:14 and given testosterone (males) or progesterone (females) or oestrogen (females). Reproductive parameters, metabolic rate and torpor variables were measured. Body mass and tail widths (fattening indicator) in males were significantly affected by testosterone, and the effects were reversed by hormone blockers. Reproductive parameters were unaffected. Resting metabolic rate and ability to use torpor were not affected by treatment in males, however torpor characteristics, especially torpor bout duration, were affected by presence of testosterone in males. In females, body mass was unaffected by hormone presence, although tail widths were affected. Disruption of reproductive cycles occurred with hormone blockers in females, however, resting metabolic rate was not affected, and only presence of progesterone affected torpor characteristics in females. Our results differ from those found for rodents, where presence of testosterone abolishes the use of torpor in males, and oestrogen inhibits torpor use in females. Our study suggests that, in this mammal, metabolic responses to the presence or absence of reproductive hormones differs between males and females, and there is no absolute endocrinologically-driven reproductive season demarcated from the torpor season.
... context, the fact that the majority of model animals used in psychiatric research are nocturnal mice and rats may hinder the development of such a model as circadian rhythms, behavior and physiology differ in many ways between nocturnal and diurnal animals including humans (Lee and Labyak 1995, 1997; Redlin 2001; Smale et al. 2003, 2005, 2008; Challet 2007). We have previously proposed that because of the differences in circadian physiology between nocturnal and diurnal animals (Kronfeld-Schor and Dayan 2003, 2008; Smale et al. 2003, 2008; Challet 2007; Cuesta et al. 2009) and because of the critical importance of circadian rhythms in affective disorders (Monteleone and Maj 2008; Kripke et al. 2009; Kronfeld-Schor and Einat 2012), models based on diurnal animals might be more appropriate for use in the research of circadian-related domains of these disorders (Einat and Kronfeld-Schor 2009; Flaisher-Grinberg et al. 2010). ...
Article
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The lack of appropriate animal models for affective disorders is a major factor hindering better understanding of the underlying pathologies and the development of more efficacious treatments. Because circadian rhythms play an important role in affective disorders, we recently suggested that diurnal rodents can be advantageous as model animals. We found that in diurnal rodents, short photoperiod induces depression- and anxiety-like behaviors, with similarities to human seasonal affective disorder. In a pilot study we also found that these behaviors are ameliorated by morning bright light administration. In the present study we further evaluated the effects of morning and evening bright light administration on short photoperiod-induced depression- and anxiety-like behaviors in diurnal fat sand rats. Animals were maintained under short (5L:19D) or neutral (12L:12D) photoperiod and treated with morning or evening bright light or red dim light as control. Morning bright light ameliorated the behavioral deficits in the elevated plus maze and social interaction tests whereas evening bright light was effective only in the social interaction test. This is the first detailed presentation of the effects of bright light treatment in an animal model and a clear demonstration to the advantages of utilizing diurnal rodents to study interactions between circadian rhythms and affect.
... The raised activity during pregnancy may be associated with the physiological features of pregnancy. Several studies on different species have shown that changes in sex hormones during mating, pregnancy, and lactation can alter an animal's circadian activity rhythm (Kiddy 1977;Labyak and Lee 1995;Wollnik and Turek 1988;Lightfoot 2008). Studies on female golden hamsters (Mesocricetus auratus) have shown that changes in hormone (estradiol and progesterone) levels during pregnancy impact the circadian locomotor rhythms (Takahashi and Menaker 1980). ...
Article
Pregnancy and parturition are often difficult to detect in wild-living animals, especially in species that give birth to altricial young in burrows or caves. Current methods to detect pregnancy and birth in hibernating animals often entail disturbances that can affect the animals' reproductive success. We developed a new method to confirm pregnancy and parturition in hibernating brown bears (Ursus arctos) using activity data recorded in dual-axis motion sensors mounted on GPS–GSM neck collars on 30 brown bears during 52 hibernation seasons in Sweden. We adjusted recorded activity to the individual basal activity level for each bear. Pregnant females showed characteristic activity patterns during the period of pregnancy, with significantly higher daily activity levels and frequency of active periods during pregnancy than nonpregnant bears. Pregnant females were active on average 2.20 times more often during the pregnancy period than during the postpartum period, compared with 0.97 times for nonpregnant females. A pregnancy index was defined as the average of the proportion of mean daily activity levels and the proportion of activity events during the pregnancy period compared with the postpartum period. It averaged 2.61 ± 1.73 (SD) for pregnant females and 0.94 ± 0.24 for nonpregnant females. Using this method, we evaluated a group of adult females that had an unverified reproductive status but were classified as not pregnant because no cubs had been observed after den emergence. The results suggested that 35 % of those females had, in fact, been pregnant.
... The multiple rhythms that some mole-rats displayed are much more challenging to explain. Various biological rhythms exist within the body, from activity rhythms to hormone rhythms [51,53,54] and any number of these biological rhythms could be associated with or even responsible for the multiple T b rhythms observed in our study, but it is unclear why these rhythms would only be found in some individuals. Some individuals displayed diurnal activity patterns whereas others displayed nocturnal activity patterns, while others still switched between patterns within a cycle. ...
Article
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Body temperature (T(b)) is an important physiological component that affects endotherms from the cellular to whole organism level, but measurements of T(b) in the field have been noticeably skewed towards heterothermic species and seasonal comparisons are largely lacking. Thus, we investigated patterns of T(b) patterns in a homeothermic, free-ranging small mammal, the Damaraland mole-rat (Fukomys damarensis) during both the summer and winter. Variation in T(b) was significantly greater during winter than summer, and greater among males than females. Interestingly, body mass had only a small effect on variation in T(b) and there was no consistent pattern relating ambient temperature to variation in T(b). Generally speaking, it appears that variation in T(b) patterns varies between seasons in much the same way as in heterothermic species, just to a lesser degree. Both cosinor analysis and Fast Fourier Transform analysis revealed substantial individual variation in T(b) rhythms, even within a single colony. Some individuals had no T(b) rhythms, while others appeared to exhibit multiple rhythms. These data corroborate previous laboratory work showing multiplicity of rhythms in mole-rats and suggest the variation seen in the laboratory is a true indicator of the variation seen in the wild.
... The important point, though, is that the differences, even when present, were small. This is perhaps surprising, given the diversity of sex hormones and of their regulation between genders, the sexual dimorphism in some anatomical and functional features of the SCN (Swaab et al., 1985), the expected estrous influence on the circadian pattern (Labiak and Lee, 1995, for additional references) and on the thermoregulatory processes (Gordon, 1993a), and the fact that hormone secretions are controlled by, and feedback to, the SCN. Krizo and Mintz (2015), in reviewing the inconsistent results of experimental ovariectomy, castration or sex hormonal replacement in rodents, commented 'it is remarkable that sex differences [on circadian patterns] are so small, given the considerable influence of gonadal steroids on the circadian period'. ...
Article
Circadian patterns are at the core of many physiological processes, and their disruption can have short- and long-term consequences. This essay focuses on one of the best known patterns, the daily oscillation of body temperature (Tb), and the possibility of its difference between genders. From human and animal studies globally considered, the tentative conclusion is reached that differences in Tb circadian pattern between genders are very small and probably limited to the timing of the Rhythm, not to its amplitude. Such similarity between genders, despite the differences in hormonal systems, presumably testifies to the importance that the Tb circadian pattern plays in the economy of the organism and its survival against environmental challenges. The second part of the article presents some previously unpublished experimental data from behaving male and female rats during hypoxia in synchronized conditions. In adult rats hypoxia (10.5% O2 for three days) caused a profound drop of the Tb daily oscillations; by day 3 they were 55% (♀) and 22% (♂) of the normoxic amplitudes, with a statistically significant gender difference. In pre-puberty rats (26-day old) hypoxia caused a major disruption of the circadian pattern qualitatively similar to the adults but not different between genders. Hence, on the basis of this preliminary set of data, it seems that sex-hormones may be a factor in how the Tb daily pattern responds to hypoxia. The implications of the effects of hypoxia on the circadian patterns, and the possibility that such effects may differ between genders, are matters that could have biological and clinical implications and deserve further investigations.
... A possible explanation for this observation could be that changes in the hormonal profile during the estrous cycle influence the thermoregulation of females. Baker et al. (1994) demonstrated that heat-stressed rats receiving estrogen showed higher evaporative heat loss and lower core temperature than their untreated counterparts; differences in core temperatures among estrogen-treated and untreated females became evident after 30 min of exposure to an air temperature of 38 � C. Labyak and Lee (1995) found that the activity patterns and core temperature of the diurnal rodent Octodon degus are affected by the estrous cycle phase; on the day of estrus, females become more active and their core temperature rises 0.4 � C compared to proestrus. The punctual divergence between the rectal temperatures of females and males recorded at 1100 h might also be a result of the numerous interactions with the thermal environment, as reported for other rodents (Dzenda et al., 2011a;b). ...
Article
The aim of this work was to investigate the thermal biology of the Spix's yellow-toothed cavy (Galea spixii) from the hot and dry environment of the Brazilian Caatinga by infrared thermography and biophysical equations. We monitored the rectal temperature, as well as the non-evaporative (radiative and convective pathways) and evapo-rative heat exchanges of males and females. The mean rectal temperature of females and males was 37.58 ± 0.02 and 37.47 ± 0.02 °C, respectively. We identified thermal windows by infrared thermography. The surface temperatures and the long-wave radiation heat exchanges were higher in the periocular, preocular, pinnae and vib-rissae regions, in that order. The surface temperature of the periocular and preocular regions correlated positively with rectal temperature. Convective heat exchange was insignificant for thermoregulation by G. spixii. Evapora-tive heat loss increased when the thermal environment inhibited the radiative pathway. Females showed higher evaporative thermolysis than males at times of greater thermal challenge, suggesting a lower tolerance to heat stress. Therefore, infrared thermography identified the thermal windows, which represented the first line of defense against overheating in G. spixii. The periocular and preocular surface temperatures could be used as predic-tors of the thermal state of G. spixii.
... Despite an effect of GDX on sex difference in hamsters, the phase angle was shown not to fluctuate across the estrous cycle in females (Davis et al., 1983). However, female degus have an earlier activity onset in estrus than in metestrus (Labyak and Lee, 1995). Similarly, in rats, the activity onset of females in estrus was shown to be prior the start of the dark period, whereas in the other phases, it generally occurs after the dark period onset Wollnik and Turek, 1988). ...
Article
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Sleep is a vital part of our lives as it is required to maintain health and optimal cognition. In humans, sex differences are relatively well-established for many sleep phenotypes. However, precise differences in sleep phenotypes between male and female rodents are less documented. The main goal of this article is to review sex differences in sleep architecture and electroencephalographic (EEG) activity during wakefulness and sleep in rodents. The effects of acute sleep deprivation on sleep duration and EEG activity in male and female rodents will also be covered, in addition to sex differences in specific circadian phenotypes. When possible, the contribution of the female estrous cycle to the observed differences between males and females will be described. In general, male rodents spend more time in non-rapid eye movement sleep (NREMS) in comparison to females, while other differences between sexes in sleep phenotypes are species- and estrous cycle phase-dependent. Altogether, the review illustrates the need for a sex-based perspective in basic sleep and circadian research, including the consideration of sex chromosomes and gonadal hormones in sleep and circadian phenotypes.
... However, sex differences do not appear until puberty is complete (Lee, 2004), because gonadal hormones modulate the circadian system during adolescent development and provide a post-pubertal sexual differentiation of the SCN (Hummer et al., 2007). In fact, the estrous cycle has a strong influence on the activity patterns of females (for more detail please see the work of Labyak & Lee, 1995). ...
Article
Integrating the multifactorial processes co-occurring in both physiological and pathological human conditions still remains one of the main challenges in translational investigation. Moreover, the impact of age-associated disorders has increased, which underlines the urgent need to find a feasible model that could help in the development of successful therapies. In this sense, the Octodon degus has been indicated as a 'natural' model in many biomedical areas, especially in ageing. This rodent shows complex social interactions and high sensi-tiveness to early-stressful events, which have been used to investigate neurodevelopmental processes. Interestingly , a high genetic similarity with some key proteins implicated in human diseases, such as apolipoprotein-E, β-amyloid or insulin, has been demonstrated. On the other hand, the fact that this animal is diurnal has provided important contribution in the field of circadian biology. Concerning age-related diseases, this rodent could be a good model of multimorbidity since it naturally develops cognitive decline, neurodegenerative histopathological hallmarks, visual degeneration, type II diabetes, endocrinological and metabolic dysfunctions, neoplasias and kidneys alterations. In this review we have collected and summarized the studies performed on the Octodon degus through the years that support its use as a model for biomedical research, with a special focus on ageing.
... However, sex differences do not appear until puberty is complete (Lee, 2004), because gonadal hormones modulate the circadian system during adolescent development and provide a post-pubertal sexual differentiation of the SCN (Hummer et al., 2007). In fact, the estrous cycle has a strong influence on the activity patterns of females (for more detail please see the work of Labyak & Lee, 1995). ...
Article
Integrating the multifactorial processes co-occurring in both physiological and pathological human conditions still remains one of the main challenges in translational investigation. Moreover, the impact of age-associated disorders has increased, which underlines the urgent need to find a feasible model that could help in the development of successful therapies. In this sense, the Octodon degus has been indicated as a ‘natural’ model in many biomedical areas, especially in ageing. This rodent shows complex social interactions and high sensi-tiveness to early-stressful events, which have been used to investigate neurodevelopmental processes. Interest-ingly, a high genetic similarity with some key proteins implicated in human diseases, such as apolipoprotein-E, β-amyloid or insulin, has been demonstrated. On the other hand, the fact that this animal is diurnal has provided important contribution in the field of circadian biology. Concerning age-related diseases, this rodent could be a good model of multimorbidity since it naturally develops cognitive decline, neurodegenerative histopathological hallmarks, visual degeneration, type II diabetes, endocrinological and metabolic dysfunctions, neoplasias and kidneys alterations. In this review we have collected and summarized the studies performed on the Octodon degus through the years that support its use as a model for biomedical research, with a special focus on ageing.
... La différence entre les sexes est aussi probablement liée à des hormones sexuelles, car elle se manifeste à la puberté et s'efface après la ménopause. De plus, des études sur des rongeurs femelles ont clairement montré que la période circadienne endogène varie en fonction du cycle reproducteur (Labyak et Lee, 1995). Les différences génétiques 3.1.4.4 La qualité et la structure du sommeil, ainsi que la qualité de la veille, peuvent dépendre aussi de facteurs génétiquement déterminés. ...
Article
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Introduction L’Anses a été saisie en 2011 pour procéder à une évaluation des risques sanitaires pour les professionnels exposés à des horaires atypiques, notamment ceux soumis à un travail de nuit habituel, qu’il soit régulier ou non. Elle a mis en place un groupe de travail multidisciplinaire pour la réalisation de cette expertise. Objectifs L’objectif principal était de statuer sur l’ensemble des effets sanitaires liés au travail de nuit en s’appuyant principalement sur une analyse critique et une synthèse des données publiées dans la littérature. Méthode L’expertise s’est appuyée sur un examen approfondi des données obtenues chez l’homme, notamment à partir d’études épidémiologiques et expérimentales publiées principalement depuis 2010. Le niveau de preuve apporté par ces études a été établi pour chacun des effets sanitaires étudiés. Résultats Les résultats de l’expertise mettent en évidence : des effets avérés sur la somnolence, la qualité de sommeil et la réduction du temps de sommeil total, ainsi que sur les métabolismes (syndrome métabolique) ; des effets probables sur la santé psychique, les performances cognitives, l’obésité et la prise de poids, le diabète de type 2 et les maladies coronariennes (ischémie coronaire et infarctus du myocarde) ; des effets possibles sur les dyslipidémies, l’hypertension artérielle et les accidents vasculaires cérébraux ischémiques. Le groupe de travail conclut à un effet probable du travail de nuit sur le risque de cancer, notamment à partir des données épidémiologiques sur le cancer du sein et des données mécanistiques. L’expertise souligne les mécanismes physiopathologiques, en particulier la disruption circadienne et les troubles du sommeil qui peuvent expliquer les effets sanitaires à long terme. Conclusions Les recommandations générales pour la prévention s’appuient sur trois axes : les modifications du système horaire pour limiter les perturbations circadiennes et du sommeil, et donc les impacts sur la vie professionnelle et personnelle ; les actions sur les conditions de travail et le contenu du travail afin de ne pas amplifier les effets des horaires de nuit et postés ; les actions sur les parcours professionnels et la gestion des ressources humaines afin de maîtriser la durée d’exposition des travailleurs.
... Estrogen inhibiting myocardial fibrosis induced by Ang II stimulation may be related to circadian rhythms and physiological processes of ion channels, and act through circadian rhythms, FGFR binding and activation, extracellular matrix release, PI3K/AKT, and potassium channel-related pathways. Animal studies have shown that E2 plays a significant role in the regulation of circadian rhythm and activity levels, and serum E2 levels in systemic circulation are consistent with circadian rhythm changes [41][42][43]. In this study, among differentially expressed mRNA in the OVX group VS the sham group, function cluster analysis showed that 4 of the top 10 molecular terms and 7 of the top 30 prediction pathways were all related to circadian rhythm, which merits we should further study. ...
Article
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Estrogen is a vascular protection factor and plays a protective role in the pathogenesis of gender differences in cardiovascular diseases. This study was to address the possible mechanisms that may explain the relationship between estradiol configuration—17β-estradiol (E2) and ventricular remodeling. Here, we show that a total of 1499 LncRNAs and 680 mRNAs significantly differently expressed were identified. This result indicates that estradiol has a global role in regulating heart gene expression profiles in female mice. Go and Pathway functional cluster analysis showed that the antagonism of E2 on cardiac remodeling and AngII-induced pathological changes in female mice may be related to physiological processes such as circadian rhythm disorder and ion channel dysfunction. Graphical Abstract
... Recent reports have described the gross anatomy and associated physiology of the reproductive tract in other hystricomorphs, including degus, but there is still a lack of histologic interpretation to support these findings. [3][4][5][6][7][8][9][10][11] The overall objective of this study was to evaluate and improve current recommended techniques for castrating male degus (Octodon degus): (1) prescrotal open technique and (2) scrotal open technique in males. 12,13 The authors also evaluated a bilateral flank (dorsolateral) approach, similar to that described in related small companion mammals, to successfully perform ovariectomies in females. ...
Article
In this study, 2 previously described surgical techniques for performing an orchiectomy in the adult male degu (Octodon degus) were evaluated: (1) prescrotal open technique and (2) scrotal open technique. Additionally, an ovariectomy procedure was assessed in female degus using the bilateral (dorsolateral) technique similar to that performed in related species. Twenty two animals (n = 14 males; 8 females) from a local small mammal shelter group, that were presented for routine surgical castration for population control measures, were included in this study. There was a significant difference in mean surgical time for the prescrotal and scrotal approach of 16.46 ± 4.28 and 23.83 ± 2.09 minutes, respectively. No significant differences were noted on anesthesia and recovery times for the orchiectomy procedures. Overall, the prescrotal approach was a faster procedure and required less anesthesia time. One male degu undergoing the scrotal open technique died during surgery, this was believed to be related to anesthesia complications (increased saliva secretions). No other complications were reported perioperatively in any other animals. All animals were observed to have sufficient pain management using an in-house visual analogue scale. The bilateral flank (dorsolateral) ovariectomy approach in female degus yielded a short total procedure time with no adverse events. No over grooming and or self-injurious behaviors were reported during both the 24 hours and 14 days recheck examinations.
... Aschoff (1979) reviewed work showing a shorter period in male chaffinches, but no sex difference in the house sparrow or pocket mouse. In the diurnal rodent Octodon degus, males had a shorter s than females (Hummer et al., 2007;Labyak and Lee, 1995;Lee and Labyak, 1997). Presumably, latitude and other selection pressures contribute to differences in s. ...
Article
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The endogenous, free-running circadian period (τ) determines the phase relationship that an organism assumes when entrained to the 24-h day. We found a shorter circadian period in African Americans compared to non-Hispanic European Americans (24.07 versus 24.33 h). We speculate that a short circadian period, closer to 24 h, was advantageous to humans living around the equator, but when humans migrated North out of Africa, where the photoperiod changes with seasons, natural selection favoured people with longer circadian periods. Recently, in evolutionary terms, immigrants came from Europe and Africa to America (‘the New World’). The Europeans were descendents of people who had lived in Europe for thousands of years with changing photoperiods (and presumably longer periods), whereas Africans had ancestors who had always lived around the equator (with shorter periods). It may have been advantageous to have a longer circadian period while living in Europe early in the evolution of humans. In our modern world, however, it is better to have a shorter period, because it helps make our circadian rhythms earlier, which is adaptive in our early-bird-dominated society. European American women had a shorter circadian period than men (24.24 versus 24.41), but there was no sex difference in African Americans (24.07 for both men and women). We speculate that selection pressures in Europe made men develop a slightly longer period than women to help them track dawn which could be useful for hunters, but less important for women as gatherers.
... Degus in the wild are diurnal, exhibiting a bimodal pattern of intensity with prominent peaks at dawn and dusk during the summer and with a continuous pattern throughout the midday during the shorter days of winter when environmental temperature does not inhibit midday activity. 31,32 Laboratory studies show similar patterns, [33][34][35][36][37][38] with some studies demonstrating bimodality 39 and others reporting predominantly unimodality. 40 Similar to observations on Mongolian gerbils, at least two investigations have reported degus to become nocturnal in the laboratory simply upon gaining access to a running wheel. ...
Article
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Although inbred domesticated strains of rats and mice serve as traditional mammalian animal models in biomedical research, the nocturnal habits of these rodents make them inappropriate for research that requires a model with human-like diurnal activity rhythms. We conducted a literature review and recorded locomotor activity data from four rodent species that are generally considered to be diurnally active, the Mongolian gerbil (Meriones unguiculatus), the degu (Octodon degus), the African (Nile) grass rat (Arvicanthis niloticus), and the antelope ground squirrel (Ammospermophilus leucurus). Our data collected under 12-hour light/dark cycles confirmed and expanded the existing literature in showing that the activity rhythms of antelope ground squirrels and African grass rats are stronger and more concentrated in the light phase of the light/dark cycle than the activity rhythms of Mongolian gerbils and degus, making the former two species preferable and more reliable as models of consistent diurnal activity in the laboratory. Among the two more strongly diurnal species, antelope ground squirrels are more exclusively diurnal and have more robust activity rhythms than African grass rats. Although animals of these two species are not currently available from commercial suppliers, African grass rats are indigenous to a wide area across the north of Africa and thus available to researchers in the eastern hemisphere, whereas antelope ground squirrels can be found throughout much of western North America’s desert country and, therefore, are more easily accessible to North American researchers.
Article
Circadian rhythms are modulated by steroid hormones, however, the mechanisms of this action are not fully understood, particularly in males. In females estradiol regulates activity level, pattern of expression, and free running period (tau). We tested the hypothesis that activity level and distribution in male mice includes both classical and "non-classical" actions of estrogens at the estrogen receptor subtype 1 (ESR1). We used transgenic mice with mutations in their estrogen response pathways: ESR1 knock-out (ERKO) mice lack the ability to respond to estrogens via ESR1. "Non-classical" estrogen receptor knock-in (NERKI) mice have an inserted ESR1 receptor with a mutation in the estrogen-response-element binding domain, allowing activation via non-genomic and second messenger pathways. Gonadectomized male NERKI, ERKO, and wildtype (WT) littermates were given oil, or low or high dose estradiol and daily activity parameters were quantified. Estradiol shortened the ratio of activity in the light relative to dark (LD ratio), shortened tau, advanced the time of activity onset, and altered responsiveness to light cues administered in the late subjective night, suggesting modulation by an ESR1-independent mechanism. Estradiol treatment in NERKI but not WT males altered the timing of activity onset, LD ratio, and the behavioral response to light cues. These results may represent disruptions in the balance of genomic/nongenomic or ESR1/ESR2 signaling pathways. We also found a significant genotype effect on total activity, LD ratio, tau, and activity duration. These data provide new information about the role of ESR1-dependent and independent signaling pathways on the timekeeping system in male mice. Copyright © 2015. Published by Elsevier B.V.
Article
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The Octodon degus, or degu, is an excellent animal model for studying the theoretical and neural underpinnings of diurnality. The power of this model comes from their unique evolutionary lineage, long lives, and relative ease of care in the laboratory for a non-domesticated species. We have summarized the field and laboratory data indicating the critical variables that influence the degus' phase preference and the possible mechanisms for the phase flexibility observed in the field and laboratory. We also review studies examining the physiology and anatomy of light and non-photic inputs to the degu circadian system and studies of the circadian pacemaker itself, with particular emphasis placed on characteristics that appear to be convergent adaptations to a diurnal niche. Finally, we begin to seek the origin for the diurnally-phased activity output of the degu, although we conclude that significant work remains to be done.
Chapter
There is a growing concern in relation to the problem of insufficient sleep, particularly in the United States. In the early 1990s a Congressionally mandated commission noted that insufficient sleep is a major contributor to catastrophic events, such as Chernobyl and the Exxon Valdez, as well as personal tragedies, such as automobile accidents. Adolescents appear to be among the most sleep-deprived populations in our society, though they are rarely included in sleep assessments. This book explores the genesis and development of sleep patterns in adolenscents. It examines biological and cultural factors that influence sleep patterns, presents risks associated with lack of sleep, and reveals the effects of environmental factors such as work and school schedules on sleep. Originally published in 2002, Adolescent Sleep Patterns will appeal to psychologists and sociologists of adolescence who have not yet considered the important role of sleep in the lives of our youth.
Article
The free-running circadian period is approximately 30 min shorter in adult male than in adult female Octodon degus. The sex difference emerges after puberty, resulting from a shortened free-running circadian period in males. Castration before puberty prevents the emergence of the sex difference, but it is not a function of circulating gonadal hormones as such, because castration later in life does not affect free-running circadian period. The aim of this study was to determine whether or not the shortening of the free-running circadian period in male degus results from exposure to gonadal hormones after puberty. We hypothesized that masculinization of the circadian period results from an organizational effect of androgen exposure during a post-pubertal sensitive period. Male degus were castrated before puberty and implanted with capsules filled with dihydrotestosterone (DHT), 17β-estradiol (E2) or empty capsules at one of three ages: peri-puberty (2-7 months), post-puberty (7-12 months), or adulthood (14-19 months). Long-term exposure to DHT or E2 did not result in a shortened free-running circadian period when administered at 2-7 or 14-19 months of age. However, E2 treatment from 7 to 12 months of age decreased the free-running circadian period in castrated males. This result was replicated in a subsequent experiment in which E2 treatment was limited to 8-12 months of age. E2 treatment at 7-12 months of age had no effect on the free-running circadian period in ovariectomized females. Thus, there appears to be a post-pubertal sensitive period for sexual differentiation of the circadian system of degus, during which E2 exposure decreases the free-running circadian period in males. These data demonstrate that gonadal hormones can act during adolescent development to permanently alter the circadian system.
Chapter
There is a growing concern in relation to the problem of insufficient sleep, particularly in the United States. In the early 1990s a Congressionally mandated commission noted that insufficient sleep is a major contributor to catastrophic events, such as Chernobyl and the Exxon Valdez, as well as personal tragedies, such as automobile accidents. Adolescents appear to be among the most sleep-deprived populations in our society, though they are rarely included in sleep assessments. This book explores the genesis and development of sleep patterns in adolenscents. It examines biological and cultural factors that influence sleep patterns, presents risks associated with lack of sleep, and reveals the effects of environmental factors such as work and school schedules on sleep. Originally published in 2002, Adolescent Sleep Patterns will appeal to psychologists and sociologists of adolescence who have not yet considered the important role of sleep in the lives of our youth.
Chapter
There is a growing concern in relation to the problem of insufficient sleep, particularly in the United States. In the early 1990s a Congressionally mandated commission noted that insufficient sleep is a major contributor to catastrophic events, such as Chernobyl and the Exxon Valdez, as well as personal tragedies, such as automobile accidents. Adolescents appear to be among the most sleep-deprived populations in our society, though they are rarely included in sleep assessments. This book explores the genesis and development of sleep patterns in adolenscents. It examines biological and cultural factors that influence sleep patterns, presents risks associated with lack of sleep, and reveals the effects of environmental factors such as work and school schedules on sleep. Originally published in 2002, Adolescent Sleep Patterns will appeal to psychologists and sociologists of adolescence who have not yet considered the important role of sleep in the lives of our youth.
Article
Previous studies paired diurnal Octodon degus undergoing/phase advances (phase-shifters) with those entrained to a light-dark (LD) cycle (donors). Results included opposite outcomes of male and female social cues on resynchronization following 6-h advances in females, but no effect of social cues on male resynchronization. The first experiment determined if social cues could influence resynchronization rates of circadian rhythms in male and female degus following a 6-h phase delay of the LD cycle. Female phase-shifters resynchronized temperature and activity rhythms 20–35% faster when housed with either entrained (donor) females or males compared with females housed alone. No significant differences in resynchronization rate for phase-shifting males existed between test conditions. This experiment extends the previous finding that females, but not males, respond strongly to donor cues to increase resynchronization rates in the presence of light. A second experiment determined that accelerated resynchronization rates of female phase-shifters housed with female donors were due to social cues directly affecting the circadian system rather than the result of social masking. On the day following resynchronization with or without a female donor present, phaseshifters were transferred individually to constant conditions (DD). The temperature and activity rhythms of female phase-shifters free-ran from the point at which resynchronization occurred for both the control and experimental females. Thus, social cues accelerate true reentrainment, not masking, of the circadian system in the presence of a LD cycle in female degus. Donor cues from females enhance reentrainment after advances and delays, but the effect of male donor cues is dependent on the direction of the phase shift.
Article
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Compelling reasons to study the role of sex in the circadian system include the higher rates of sleep disorders in women than in men and evidence that sex steroids modulate circadian control of locomotor activity. To address the issue of sex differences in the circadian system, we examined daily and circadian rhythms in wheel-running activity, electrical activity within the suprachiasmatic nucleus, and PER2::LUC-driven bioluminescence of gonadally-intact adult male and female C57BL/6J mice. We observed greater precision of activity onset in 12-hour light, 12-hour dark cycle for male mice, longer activity duration in 24 hours of constant darkness for female mice, and phase-delayed PER2::LUC bioluminescence rhythm in female pituitary and liver. Next, in order to investigate whether sex differences in behavior are sex chromosome or gonadal sex dependent, we used the 4 core genotypes (FCG) mouse model, in which sex chromosome complement is independent of gonadal phenotype. Gonadal males had more androgen receptor expression in the suprachiasmatic nucleus and behaviorally reduced photic phase shift response compared with gonadal female FCG mice. Removal of circulating gonadal hormones in adults, to test activational vs organizational effects of sex revealed that XX animals have longer activity duration than XY animals regardless of gonadal phenotype. Additionally, we observed that the activational effects of gonadal hormones were more important for regulating activity levels in gonadal male mice than in gonadal female FCG mice. Taken together, sex differences in the circadian rhythms of activity, neuronal physiology, and gene expression were subtle but provide important clues for understanding the pathophysiology of the circadian system.
Chapter
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This chapter reveals that rhythms are advantageous for survival of the organism. There is an optimal time of the day for animals to forage for food. Likewise, the safest time to be active is when predators are not active. A biological mechanism that synchronizes and coordinates internal physiological events with the external environment prepares the organism for predictable environmental changes, especially when an animal is removed from direct external cues, as when it is sleeping in its burrow. Furthermore, all of the energetic requirements of the body cannot be simultaneously fulfilled, and peaks in energetic processes must be partitioned throughout the day. Circadian rhythms permit bodily functions to assume an appropriate temporal niche. From an evolutionary and adaptive perspective, animals have evolved to synchronize circadian rhythms with the environment to promote survival.
Article
Trinomys yonenagae (Rocha, 1995), Yonenaga's Atlantic spiny-rat, is a small caviomorph rodent locally known as "rabo-de-facho" (Portuguese) due to its setiform hairs and long penciled tail. It is endemic to the sand dune field of the arid Brazilian Caatinga, on the west side of the Middle São Francisco River, from Barra to Pilão Arcado (Bahia, Brazil). The long hind feet, the fossorial and colonial habits, and the inflated tympanic bullae are cited as adaptations to the hot and sandy habitat. One of 10 species in the genus, it is listed as "Endangered" by the International Union for Conservation of Nature and Natural Resources because it is found only at a single location of less than 5,000 km 2 and its habitat continues to decline due to the extraction of sand.
Article
Steroid hormones including estrogens modulate the expression of daily activity and circadian rhythms, including free-running period, phase angle of activity onset, and response to light. The mechanisms underlying these effects, however, are not fully understood. We tested the hypothesis that estrogen signaling is required for photic responsiveness of the circadian timing system. We used estrogen receptor subtype 1 (ESR1) knock-out mice (ERKO) and nonclassic estrogen receptor knock-in mice (NERKI). ERKO animals are unable to respond to estrogen at ESR1, and NERKI animals lack the ability to respond to estrogens via estrogen response element-mediated transcription but still respond via nonclassical mechanisms. We analyzed behavioral shifts in activity onset in response to 1-h light pulses given across the subjective 24-h day in gonadally intact male and female NERKI, ERKO, and wild-type (WT) littermates. We also examined Fos protein expression in the suprachiasmatic nucleus, the site of the master circadian pacemaker, at 2 times of day. We found a significant effect of genotype on phase shifts in response to light pulses given in the subjective night. Female WT mice had a significantly larger phase response than ERKO females during the early subjective night (phase shift of 98 min and 58 min, respectively; p < 0.05). NERKI females were intermediate to WT and ERKO females, suggesting a contribution of nonclassical estrogen signaling on circadian timekeeping functions. This genotype effect is not observed in males; they did not have a difference in phase shifts following a light pulse at any time point. WT males, however, shifted an average of 47 min less than did females at zeitgeber time (ZT) 16 (ZT 0 lights-on and ZT 12 lights-off). These data indicate that estrogens modify the response of the circadian timekeeping system to light via classical and nonclassical signaling pathways.
Chapter
There is a growing concern in relation to the problem of insufficient sleep, particularly in the United States. In the early 1990s a Congressionally mandated commission noted that insufficient sleep is a major contributor to catastrophic events, such as Chernobyl and the Exxon Valdez, as well as personal tragedies, such as automobile accidents. Adolescents appear to be among the most sleep-deprived populations in our society, though they are rarely included in sleep assessments. This book explores the genesis and development of sleep patterns in adolenscents. It examines biological and cultural factors that influence sleep patterns, presents risks associated with lack of sleep, and reveals the effects of environmental factors such as work and school schedules on sleep. Originally published in 2002, Adolescent Sleep Patterns will appeal to psychologists and sociologists of adolescence who have not yet considered the important role of sleep in the lives of our youth.
Article
Mongolian gerbils are territorial and live in family groups with established, stable male-female pairs. The objectives of this study were to investigate whether locomotor activity indicates female receptivity, and to evaluate the impact of a male on the stability of the female sexual cycle. To prevent gravidity, males were sterilised by vasectomy. Nevertheless, they behaved like intact males, displayed copulatory behaviour, and had normal mean serum testosterone levels of 1.1±0.2 ng/ml. Oestrus caused modulations in the activity pattern and hence influenced locomotor activity; female receptivity was reflected by an advance in the onset of activity. Male presence led to prolonged and irregular oestrus cycles in females. Three pairs were stable and nearly no attacks occurred for nine months. However, in four pairs, females suddenly attacked males. Males displayed flight and appeasement behaviours, but two died within 24 hours, and two were severely injured and had to be separated. Two of these females were paired again to other vasectomised males, but killed their cagemates after 3.5 and 12.5 weeks, respectively. In total, six of nine pairs were disrupted by female aggression, four males were killed and two males were separated but presumably would have otherwise died. Females presumably detected male infertility by repeated unsuccessful matings without sperm transmission and/or by physical impairments due to repeated pseudopregnancy. As a result they no longer invested in pair bonds that would eventually diminish their reproductive fitness.
Article
This article reviews the literature on the circadian rhythms of body temperature and whole-organism metabolism. The two rhythms are first described separately, each description preceded by a review of research methods. Both rhythms are generated endogenously but can be affected by exogenous factors. The relationship between the two rhythms is discussed next. In endothermic animals, modulation of metabolic activity can affect body temperature, but the rhythm of body temperature is not a mere side effect of the rhythm of metabolic thermogenesis associated with general activity. The circadian system modulates metabolic heat production to generate the body temperature rhythm, which challenges homeothermy but does not abolish it. Individual cells do not regulate their own temperature, but the relationship between circadian rhythms and metabolism at the cellular level is also discussed. Metabolism is both an output of and an input to the circadian clock, meaning that circadian rhythmicity and metabolism are intertwined in the cell.
Article
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Torpor and reproduction in mammals and birds are widely viewed as mutually exclusive processes because of opposing energetic and hormonal demands. However, the reported number of heterothermic species that express torpor during reproduction is ever increasing, to some extent because of recent work on free-ranging animals. We summarize current knowledge about those heterothermic mammals that do not express torpor during reproduction and, in contrast, examine those heterothermic birds and mammals that do use torpor during reproduction. Incompatibility between torpor and reproduction occurs mainly in high-latitude sciurid and cricetid rodents, which live in strongly seasonal, but predictably productive habitats in summer. In contrast, torpor during incubation, brooding, pregnancy, or lactation occurs in nightjars, hummingbirds, echidnas, several marsupials, tenrecs, hedgehogs, bats, carnivores, mouse lemurs, and dormice. Animals that enter torpor during reproduction often are found in unpredictable habitats, in which seasonal availability of food can be cut short by changes in weather, or are species that reproduce fully or partially during winter. Moreover, animals that use torpor during the reproductive period have relatively low reproductive costs, are largely insectivorous, carnivorous, or nectarivorous, and thus rely on food that can be unpredictable or strongly seasonal. These species with relatively unpredictable food supplies must gain an advantage by using torpor during reproduction because the main cost is an extension of the reproductive period; the benefit is increased survival of parent and offspring, and thus fitness.
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There is overwhelming evidence that the circadian timekeeping system is sensitive to gonadal hormones during perinatal development and adulthood. However, there is a noticeable lack of research in animal models focusing on circadian rhythms during puberty, a developmental window of dramatic hormonal change. This dissertation addresses this research gap using experiments in both fast-developing and slow-developing rodent species (Rattus norvegicus and Octodon degus). The results indicate that the circadian system continues to develop across the post-weaning and pubertal periods in both species in a manner that exhibits strong sex differences. In males, pubertal changes in activity rhythms were robust, involving a switch from bimodal to unimodal activity patterns as well as a 3-5 hr magnitude phase-advance of activity rhythms relative to the environmental light-dark cycle. Pre-pubertal gonadectomy diminished these changes in both species, indicating that pubertal hormones were involved in producing the changes. Overall, females showed smaller circadian phase changes than males during puberty. In the degu, these sex differences were extreme, with female degus almost completely lacking phase changes during puberty. Results suggest that pubertal hormones could act on multiple components of the circadian system. For example, preliminary data from the degu suggest that a photosensitive rhythmic component of the central circadian oscillator (Per1) exhibits phase changes during puberty that parallel phase changes in behavioral rhythms. However, pubertal rats exhibited a reorganization of activity rhythms under constant conditions, independent of photic entrainment. Thus, both the photic entrainment pathway and downstream circadian elements may be altered during puberty. Taken in tandem with growing evidence from multiple species, as well as sleep electrophysiological studies from our own lab, it appears that the processes governing daily sleep and activity rhythms continue to develop far into the pubertal period in many mammals. This conclusion is discussed in the context of the developmental ecology of these rodent species. The ramifications of these results for the wide-spread use of young animals by the scientific community for patch-clamp experiments of the circadian system are also discussed. Finally, this evidence can inform the national debate regarding teenage sleep patterns and high school start times.
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Free-running circadian rhythms in core temperature, wheel-running and general locomotor activity were studied in ovariectomized or intact female rats housed with or without access to a running wheel. No differences in the monitored parameters were found between the intact and ovariectomized rats without a wheel. In the presence of a wheel, however, the intact rats differed from those that had been ovariectomized by displaying a shorter circadian period, an increased amplitude of the temperature rhythm, and strikingly higher rates of wheel-running and general locomotor activity. After estradiol treatment, the ovariectomized rats with a wheel developed a small increase in the temperature amplitude, and also in the correlation between wheel-running and general locomotor activity; these changes were not associated with a significant increase in wheel-running or a shortening of the circadian period. We conclude that some of the differences in circadian function between intact and ovariectomized rats are due to the differential use they make of running wheels, when available, and not directly attributable to the absence or presence of gonadal steroids.
Chapter
In this, our Second Edition of Reproduction in Mammals, we are responding to numerous requests for a more up-to-date and rather more detailed treatment of the subject. The First Edition was accorded an excellent reception, but the first five books were written ten years ago and inevitably there have been advances on many fronts since then. As before, the manner of presentation is intended to make the subject matter interesting to read and readily comprehensible to undergraduates in the biological sciences, and yet with sufficient depth to provide a valued source of information to graduates engaged in both teaching and research. Our authors have been selected from among the best known in their respective fields. This volume discusses the manifold ways in which hormones control the reproductive processes in male and female mammals. The hypothalamus regulates both the anterior and posterior pituitary glands, whilst the pineal can exert a modulating influence on the hypothalamus. The pituitary gonadotrophins regulate the endocrine and gametogenic activities of the gonads, and there are important local feedback effects of hormones within the gonads themselves. Non-pregnant females display many different types of oestrous or menstrual cycles, and there are likewise great species differences in the endocrinology of pregnancy. But the hallmark of mammals is lactation, and this also exerts a major control on subsequent reproductive activity.
Article
Previous observations support the belief that the midcycle thermal shift occurs immediately after ovulation. The biphasic character of the basal body temperature during an ovarian cycle should be related to the 2 phases of secretory activity in the ovary. The opposed thermic effects of the ovarian steroids was studied in female castrates. Observations were correlated with the temperature-altering effects of estrogen and progesterone when administered during each phase of the cycle in regularly menstruating women. 26 surgically castrated and 6 intact regularly menstruating women aged 22-54 were selected for study. The bilateral oophorectomy of each of the 26 castrates had been performed by a member of the Department of Gynecology of the Graduate Hospital University of Pennsylvania. The 6 regularly menstruating women were hospital patients. The experimental facts comprised the daily waking temperature taken rectally. Ethinyl estradiol was the estrogen and pregneninolone the progesterone employed in all of the castrated subjects. 4 types of experiments were performed in the 12 castrates who took and recorded their rectal temperature daily for 2-4 months: 1) estrogen alone as administered 2) progestogen alone 3) estrogen followed by progestogen and 4) estrogen and progestogen simultaneously. Ethinyl estradiol lowered the waking temperature from .2 to .4 degrees Farenheit in 18 of 27 tests. 60 mg of pregneninolone daily raised by body temperature from .4 to .6 degrees Farenheit in 20 of 30 trials but 80 mg daily caused a slightly higher thermogenic response in 19 of 22 experiments. Successively administered ethinyl estradiol and pregneninolone resulted in an estrogen-evoked depression followed by a progestogen stimulated elevation of temperatuure in 11 of 15 attempts. The simultaneous administration of .15 mg of ethinyl estradiol and 60 mg of pregneninolone daily resulted in a slight rise of the basal body temperature in 12 of 17 trials. The temperature-depressing effect of estrogen and the thermogenic property of progestogen were demonstrated in the 6 menstruating women.
Article
Ovariectomized golden-mantled ground squirrels (Spermophilus lateralis) were implanted with estradiol benzoate (EB)-filled or empty capsules. Body weight was monitored for at least 1 yr before, during, and after hormone treatment. EB treatment of 6-7 mo duration, restricted to the weight-gain phase, decelerated weight gain and delayed attainment of peak weight by 34 days; the period of the circannual rhythm, measured between successive trough weights, was 36 days longer in squirrels treated with estradiol than in untreated animals. EB treatment of 2- to 4-mo duration, restricted to the weight-loss phase, accelerated weight loss, advanced attainment of trough weights by 57 days, and decreased the period of the circannual rhythm by 66 days. Estradiol-induced phase delays and advances were preserved in the year after discontinuation of hormone treatment. These results favor the existence of circannual phase-response curves to hormones and provide a system for pharmacological manipulation of circannual rhythms.
Article
The effects of estrous cycles, castration, subcutaneous steroid replacement, and intracranial steroid implants on the colonic temperatures were examined in 3 experiments. In Experiment 1 a rise in colonic temperature was observed at proestrus in intact females, and castration lowered the colonic temperatures of both males and females 1–2 hr before lights out. In Experiment 2 we tested the effects of 3 doses of progesterone and estradiol benzoate on the colonic temperatures of ovariectomized rats. Both hormones raised colonic temperature. The rise in colonic temperature was directly related to the progesterone dose, but it was inversely related to the dose of estradiol benzoate. In Experiment 3, progesterone and estradiol benzoate were implanted in the preoptic area of ovariectomized rats. Although estradiol benzoate in this site had no effect on colonic temperature, there was some suggestion that progesterone may increase colonic temperature when implanted in the preoptic area.
Article
Estradiol was applied directly to the striatum of ovariectomized female rats by a unilateral intracerebral cannula for three hr or four days. Following four days of estradiol treatment, rats increased the number of rotations in the direction away from the side of the hormone treatment. Cholesterol-treated animals did not change their rotational behavior. Dopamine receptors were assayed in the same animals by autoradiography; D2 receptors increased on the hormone-treated side relative to the untreated side after four days of treatment, only in the lateral striatum. D1 dopamine receptors did not change. The D2:D1 receptor ratio was related to the direction of rotation. Measurements of membrane fluidity with a fluorescent probe revealed no effect of estradiol on striatal membrane fluidity. Membrane proteins were labeled with estrogen agonist and antagonist affinity labels and analyzed by gel electrophoresis, but no saturable membrane binding sites were detected. The results indicate that estradiol acts directly in the striatum to affect behavior and dopamine receptors, but the neurochemical mechanisms remain to be determined.
Article
Adult female rats implanted with a microelectrode drive unit were trained to walk on a computer-controlled treadmill apparatus (10 s on every 20 s for 2 h) during recording of single Purkinje neurons in the paravermal area of the anterior cerebellum. Vigorous increases in the firing rate of individual units were found to be correlated with movement of specific limbs in particular stages of the step cycle during treadmill locomotion. Both spontaneous and motor-evoked discharge of individual Purkinje neurons were monitored before and after s.c. injection of either 17β estradiol (E2, 100 ng/kg) or progesterone (P, 50 μgs). The percent increase in firing rate during locomotion versus rest was determined as a measure of the evoked: spontaneous discharge ratio. Drug-induced changes in this ratio indicate differential effects on the individual parameters, rather than simple excitatory or inhibitory effects. For all neurons tested, E2 augmented the movement-evoked discharge over pre-E2 control levels. The onset for this effect occurred at 15 min post-steroid, with a peak response noted at 30–35 min post-steroid. By 60–90 min, a partial recovery of the evoked: spontaneous ratio was noted, although absolute increases in both parameters were still observed, indicating long-term effects on neuronal activity. These effects were independent of the stage of the estrous cycle. In contrast, P decreased absolute firing rates of Purkinje cells during stationary and locomotor phases. However, the evoked: spontaneous ratio was decreased to an even greater degree. The latency for this effect was 9–12 min, with recovery to control levels of response seen at 30 min post-steroid. This response was typical of cells tested on estrus and diestrus 1. Cells tested on proestrus or diestrus 2, when E2 levels are increasing, were not modulated by P using the above paradigm.
Article
The article reviews most of the data available on the period tau of freerunning circadian rhythms, measured in constant conditions. Emphasis is placed on the effects of light intensity and ambient temperature on tau, with references to influences of other external as well as internal factors. In the introduction, examples are given of spontaneous and induced variations in tau and its dependence on the experimental history. The discussion concentrates largely on results obtained from arthropods and vertebrates.
Article
Continuous administration of estradiol benzoate by means of subcutaneously implanted capsules shortened the free-running circadian period of locomotor activity of blind hamsters (Mesocricetus auratus) that had had their ovaries removed. Estradiol also advanced the phase of the wheel running of sighted female hamsters without ovaries that were entrained to a photoperiod with 12 hours of light and 12 of darkness. These results, and findings from hamsters undergoing natural estrous cycles, indicate that endogenous estradiol is involved in the regulation of circadian periodicity.
Article
Nocturnal peaks in core body temperature of rats during the estrous cycle were highest during the night of ovulation (2300-0200 h, proestrus-estrus) and lowest during the night before (diestrus 2-proestrus). Less dramatic diurnal secondary peaks, absent only during estrus, occurred 3-4 h after the onset of daylight. After induction of pseudopregnancy, mean temperature declined, but both daily peaks persisted until the first postluteal estrus, when the secondary peak was again absent transiently. Ovariectomy reduced mean core temperature and abolished all secondary peaks. In contrast, castration during pseudopregnancy did not abolish the secondary peaks. When cyclic rats were gonadectomized (abolishing the secondary rhythm) it was possible to re-establish this rhythm by stimulating the uterine cervix (as if to induce pseudopregnancy). However, in animals exposed to darkness (which also abolishes the secondary rhythm) reinduction by cervical stimulation was ineffective. These results indicated that the integrity of the secondary peak, though dependent on photoperiod, nevertheless was influenced by a neuroendocrine reflex arc.
Article
Wrist activity was monitored continuously for one year in a woman who went about her normal life. The year of data were analyzed for changes and rhythms--daily, weekly, menstrual, lunar, annual. For each day, average motions/5 minutes, activity onset, activity offset, alpha (duration of activity), and acrophase were measured. Periodograms and average daily wave forms were calculated. Well-defined, entrained, daily rest-activity cycles were observed throughout the year with periods close to 24 hours. There was weekend delay (0.7 hours) in onset, weekend decrease in alpha (1.0 hours), and weekend advance of acrophase (0.4 hours). Motions/5 minutes decreased 9%, onsets were 0.3 hours later, and alphas were 0.4 hours shorter on menstrual cycle days 8 through 18 which should have encompassed the time of ovulation. Lunar phase had no effect. Annual changes in onset (1.1 hours), offset (1.2 hours), and acrophase (1.1 hours) were attributed to the 1-hour change between standard and daylight savings time.
Article
To study the relationship between estrous and circadian periodicity, we investigated the period of the estrous cycle in two types of female golden hamsters: normals (circadian period approximately 24 h) and tau mutants (circadian period approximately 20 h). Records of running wheel activity, general locomotor activity, body temperature, vaginal secretion, and sexual receptivity of hamsters kept under constant lighting conditions indicated an estrous period of approximately 96 h for both groups of animals. The fact that animals with different circadian periods have the same estrous period suggests the existence of separate mechanisms in the control of circadian and estrous periodicity. Circadian periodicity is determined by a pacemaker located in the suprachiasmatic nuclei, whereas estrous periodicity is determined by positive and negative feedback loops involving the hypothalamus, pituitary, and gonads. Coupling of the two mechanisms takes place under at least some conditions, but additional research is necessary to elucidate the mechanisms by which this is accomplished.
Article
Ovariectomized golden-mantled ground squirrels (Spermophilus lateralis) were implanted with estradiol benzoate (EB)-filled or empty capsules. Body weight was monitored for at least 1 yr before, during, and after hormone treatment. EB treatment of 6-7 mo duration, restricted to the weight-gain phase, decelerated weight gain and delayed attainment of peak weight by 34 days; the period of the circannual rhythm, measured between successive trough weights, was 36 days longer in squirrels treated with estradiol than in untreated animals. EB treatment of 2- to 4-mo duration, restricted to the weight-loss phase, accelerated weight loss, advanced attainment of trough weights by 57 days, and decreased the period of the circannual rhythm by 66 days. Estradiol-induced phase delays and advances were preserved in the year after discontinuation of hormone treatment. These results favor the existence of circannual phase-response curves to hormones and provide a system for pharmacological manipulation of circannual rhythms.
Article
Female rats were housed in Wahmann wheels under a 12:12 light-dark (LD) photoperiod for 36 days and then were switched to LD 10:14 for 36-64 days. Running was 95-100% nocturnal. Overall amounts of running were higher in LD 12:12, but changes over the estrous cycle were similar. On the night of proestrus running increased by 64% in LD 12:12 and 123% in LD 10:14 (p less than 0.0001) compared to the first night of diestrus. Nighttime Tb's were correlated with running levels. In LD 12:12 Tb on proestrus was higher by 0.3 +/- 0.0 degrees C (p less than 0.0001); in LD 10:14 it was higher by 0.2 +/- 0.0 degrees C (p less than 0.001) compared to diestrus-1. During L, Tb was lowest on proestrus and highest on estrus. Half of the rats exhibited a consistent phase advance of at least 30 min in both Tb and activity on proestrus. The advanced Tb acrophase was correlated with both the activity acrophase (r = .91; p less than 0.0001) and the amount of running (r = .60; p less than 0.01). The wheels of 6 rats were then locked at night in LD 10:14. There were no significant Tb changes from diestrus-1 across the cycle. However, Tb acrophase was delayed a mean of 76 +/- 16 min (p less than 0.01) in these rats. Also, the Tb acrophase across all days of the estrous cycle was delayed by 94 +/- 18 min (p less than 0.001) compared to when the wheels were open.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
We tested the hypothesis that the free-running period and phase angles of entrainment of circadian locomotor activity rhythms of golden-mantled ground squirrels (Spermophilus lateralis) vary as a function of body temperature (Tb). Animals were maintained in a light-dark cycle (LD 14:10), and at 6-week intervals ambient temperature (Ta) was changed from 20 degrees to 30 degrees C, or vice versa. Data were collected during the animals' homeothermic and heterothermic phases. Subsequently, squirrels were housed in dim constant illumination with the same alternating temperature sequence. In heterothermic ground squirrels (those capable of Tb less than 34 degrees C), a decrease in Ta from 30 degrees to 20 degrees C caused phase delays in activity onset, phase advances in activity termination, and a decrease in duration of the active phase; increases in Ta from 20 degrees to 30 degrees C produced the opposite effect on each of these parameters. The free-running period of the activity rhythm of heterothermic squirrels increased and decreased in response to 10 degrees C decreases and increases in Ta, respectively. Changes in Ta did not affect circadian parameters in homeothermic squirrels. Seasonal variations in circadian organization previously observed in this species appear to reflect the influence of endogenous fluctuations in body temperature. Tissue temperature has a major influence on circadian rhythms of golden-mantled ground squirrels.
Article
In female rats, food intake and wheel running fluctuate with the estrous cycle, creating a state of oscillating energy balance. The effect of the estrous cycle on the energy expenditure of conventionally housed rats (S) and of rats given access to an activity wheel (A) was compared. Over 24 weeks, the weight gain of the groups was similar although the body fat content of A was 30 g lower than that of S at the end of the study. During the assessment of energy expenditure by indirect calorimetry estrous cycles were disrupted and food intake and wheel running reduced. However, a correlation between expenditure and wheel running was obtained from which the cost of activity was derived (21 kJ/kg/km) and from which data were extrapolated to normal circumstances. This revealed that A, running on average 6214 rev/day, expended approximately 64 kJ/day more than S. This they compensated for by increasing their food intake by 6 g/day (70 kJ/day). Over the estrous cycle wheel running was maximal at proestrus and minimal at metestrus--the reverse trend in food intake was observed. This cyclic difference in energy balance between metestrus and proestrus was estimated to be equivalent to 23% of the 'maintenance' requirement. Thus voluntary activity bears a marked impact on day to day energy balance but has little effect in the long-term since in the female rat intake is precisely regulated to meet expenditure.
Article
With respect to the ovarian status and the estrous cycle as expressed by the vaginal cytology, it was emphasized that there is only a rough correspondence between the vaginal stages and the days of the cycle. The 4-day cycle tends to be the most frequent, with the 5-day cycle a normal variant. Spontaneous persistent vaginal estrus (SPE), an acyclic state occurring in older adult rats, reflects the presence in the ovaries of large vesicular follicles failing to luteinize and, hence, the absence of corpora lutea once the condition becomes well established. Pseudocyclic fluctuations in the vaginal smear during SPE resemble those in ovariectomized rats treated chronically with estrogen. The age of onset of SPE varies among different rat strains, appearing as early as 5 or 6 months in the DA and CD strains, but rarely before 12 months in the O-M strain. O-M/DA hybrids were intermediate. In the DA strain there was also a marked influence of length of daily illumination on the occurrence of SPE: exposure to 10 hours or less of light per day restored cycling to rats that had already shown SPE while exposed to longer days. An hereditary influence of age was also apparent in the rapidity with which continuous illumination induced persistent estrus (LLPE). Young DA females rapidly entered LLPE within 10 days, while young O-M females remained cyclic for 5 weeks. Hybrids again were intermediate. At middle age. O-M rats became as responsive as young rats of the DA strain. Like SPE in DA rats. LLPE was reversible, for estrous cycles returned after daily exposure to light was reduced. The special sensitivity of DA rats to lighting may have been a trait acquired from outcrossing with wild gray rats in years past. Normal cycling could be restored in SPE rats by daily injection of progesterone at low dosage. The same effect followed isolated treatments with progesterone upon return of proestrus/estrus after interruption of SPE. This was the first demonstration of positive feed-back of progesterone, the first sign of its biphasic action, and an indication that progesterone facilitates the action of estrogen in promoting ovulation. When progesterone treatment was delayed after proestrus/estrus there was progressively lower effectiveness during the next 10 days. Indirect support of regular ovulatory cycles resulted from treating DA SPE rats with prolactin (PRL) daily at low doses, provided that an initial set of corpora lutea was first induced by other means.(ABSTRACT TRUNCATED AT 400 WORDS)
Article
Estrous cycle-dependent variation in amphetamine (AMPH)-stimulated behaviors and striatal dopamine (DA) release were determined for freely moving rats undergoing intracerebral microdialysis. There was greater AMPH-stimulated striatal DA release in the striatum of rats in estrus, during the period from 20 min to 100 min post-AMPH, compared with the response of rats in diestrus (P less than 0.05). Animals in estrus also showed less general activity and greater intensity of stereotyped behaviors than did animals in diestrus (P less than 0.05). Independent experiments examining estrous cycle-dependent differences in AMPH-stimulated striatal DA release in vitro also found that AMPH-stimulated striatal DA release was greater on estrus than on diestrus (P less than 0.05). Thus, striatal DA release and behaviors induced by AMPH are modulated by ovarian hormones. The heightened responsiveness to AMPH during estrus suggests that estrogen and/or progesterone potentiate the striatal DA response to AMPH.
Article
Estrogen treatment alters the expression of ultradian activity rhythms in male and female LEW/Ztm rats. This finding raises the possibility that the expression of ultradian rhythms may vary on different days of the estrous cycle. To test this hypothesis, we recorded the circadian and ultradian wheel-running activity rhythms of entrained (LD 12:12) and free-running sexually mature LEW/Ztm females during their 4- or 5-day estrous cycle. The mean daily activity, the duration of activity, the circadian period of activity, and the occurrence of ultradian rhythms differed significantly among the days of the estrous cycle. In LD 12:12, the phase angle difference between the beginning of activity and light offset varied reliably in 5-day cycling animals. The highest daily mean of activity, the longest duration, and the shortest circadian period length were observed on the day of estrus in both entrained and free-running animals. The day of estrus was characterized by a constant high level of activity throughout the activity phase, while the days following ovulation showed a bi- or trimodal activity pattern. Power spectrum analysis revealed significant ultradian components for the days of metestrus and diestrus, but only circadian components for the days of proestrus and estrus. These results were interpreted as indicating that endogenous changes in circulating hormone levels can induce changes in the ultradian and circadian patterns of wheel-running activity in LEW/Ztm rats.
Article
Circadian rhythms are of endogenous origin, in humans as in all organisms. Under temporal isolation, i.e., after exclusion of all environmental time cues, circadian rhythmicity persists but with a period slightly deviating from 24 hours; in human, freerunning circadian rhythms always show periods close to 25 hours. In a minority of experiments, overt rhythms of different variables do not run in mutual synchrony but internally desynchronized in the steady state. This means that, indeed, most physiological rhythms, and particularly that of body temperature, hold a period close to 25 hours; it is mainly the sleep-wake rhythm (but also the overt rhythms of several more variables) which shows freerunning periods being considerably longer or shorter than 25 hours. This state of the rhythm is not concerned by the presence or absence of naps; rather, this state is characterized by a considerable stretching or compressing of the entire sleep-wake cycle. The period and other parameters of freerunning rhythms can be modified by continuously operating stimuli. Also the tendency toward the spontaneous occurrence of internal desynchronization does not depend only on personality data (e.g., neuroticism, or age) but also on the external conditions. Whereas constant light in the normal range of artificial illumination (intensities between 0 and 1500 lux) does not affect freerunning human circadian rhythms, the period is longer and the tendency toward internal desynchronization is higher under constant bright light (intensity greater than 3000 lux) than under constant light of normal intensity (or total darkness). This result has been confirmed with various physiological functions, e.g. the rhythms of deep body temperature and melatonin excretion. Social contacts (when subjects do not live singly isolated but in groups) or behavioral stress operates in the same direction as bright light. On the other hand, physical workload does not affect freerunning rhythms. Under natural conditions, the endogenously generated rhythms are synchronized to the 24-hour day. Under laboratory conditions (i.e., under temporal isolation), also artificial zeitgebers can be effective but only within limited ranges of periods; the width of such a range of entrainment is an indicator of the strength of the zeitgeber under consideration.(ABSTRACT TRUNCATED AT 400 WORDS)
Article
Peripheral levels of plasma estrone (E1) and estradiol (E2), as measured by RIA, showed little correspondence in the cycling hamster. A diurnal pattern of Ex was apparent during the cycle with peak levels reached at 2200. Estradiol levels were low on the first 2 days of the cycle, correlated with the absence of antral follicles, but were higher at 2200 of day 2. A peak was reached at 1400 of day 3 (approximately 90 pg/ml) and the levels remained elevated for at least 8 hr. E2 was depressed at 0900 of day 4, but this was followed by an almost linear increase between 0900 and 1500 when the highest value for the estrous cycle was attained (186.6 pg/ml). A sharp decrease, down to baseline values, followed. The day 4 peak in E2 was temporally related to the preovulatory surge in LH and an abrupt increase in ovarian progesterone. Phenobarbital (Phen) injected to day 4 cycling animals prevented the E2 peak at 1500, whereas the addition of 5 μg of LH restored E2 to normal values. However, E1 was not affected by e...
Article
The body temperature of 18 female rabbits was recorded once a day for about 3 months. Three of these rabbits demonstrated a statistically significant cyclic variation in temperature, the mean length of the cycles varying from 6 to 11 days.The observed cyclic variations persisted after ovariectomy with cyclicity appearing in two additional animals. In 6 out of 8 rabbits the mean body temperature decreased significantly upon removal of the ovaries.
Article
Progesterone has been shown to be thermogenic in a variety of species. The present studies investigated the role of the pituitary and thyroid glands in the thermogenic response to exogenous progesterone in 254 adult female rats. In intact rats, subcutaneous injections of 0.1 or 0.5 mg of progesterone daily for 14 days were ineffective in increasing rectal temperatures, whereas injections of 1.0, 2.0, 5.0 or 10.0 mg progesterone daily for 14 days increased rectal temperature by 0.3, 0.4, 0.4 and 0.5 C, respectively (p <0.05). Exogenous progesterone (5.0 mg daily) increased the rectal temperature of ovariectomized rats by 0.3 C (p <0.05). On the other hand, the rectal temperature of hypophysectomized rats was not increased by administration of progesterone. Thyroid acinar cell height was increased significantly from 7.4 to 9.3 μ by daily administration of 5.0 mg of progesterone to intact rats. Injection of 2-thiouracil (17.5 mg daily) lowered rectal temperature and blocked the thermogenic response to exogenous progesterone. However, thyroidectomy did not prevent the response to exogenous progesterone despite the fact that thyroidectomy alone significantly lowered rectal temperature from 35.4 to 34.7 C. These results indicate that the thyroid is not the mediator of the thermogenic response to progesterone, but that the pituitary is necessary for the response. (Endocrinology 86: 717, 1970) Progesterone has been shown to be thermogenic in a variety of species. The present studies investigated the role of the pituitary and thyroid glands in the thermogenic response to exogenous progesterone in 254 adult female rats. In intact rats, subcutaneous injections of 0.1 or 0.5 mg of progesterone daily for 14 days were ineffective in increasing rectal temperatures, whereas injections of 1.0, 2.0, 5.0 or 10.0 mg progesterone daily for 14 days increased rectal temperature by 0.3, 0.4, 0.4 and 0.5 C, respectively (p <0.05). Exogenous progesterone (5.0 mg daily) increased the rectal temperature of ovariectomized rats by 0.3 C (p <0.05). On the other hand, the rectal temperature of hypophysectomized rats was not increased by administration of progesterone. Thyroid acinar cell height was increased significantly from 7.4 to 9.3 μ by daily administration of 5.0 mg of progesterone to intact rats. Injection of 2-thiouracil (17.5 mg daily) lowered rectal temperature and blocked the thermogenic response to exogenous progesterone. However, thyroidectomy did not prevent the response to exogenous progesterone despite the fact that thyroidectomy alone significantly lowered rectal temperature from 35.4 to 34.7 C. These results indicate that the thyroid is not the mediator of the thermogenic response to progesterone, but that the pituitary is necessary for the response. (Endocrinology 86: 717, 1970)
Article
Wheel-running and direct observation of animals in their home cages were used to measure the activity of golden hamsters through the oestrous cycle, pregnancy and pseudopregnancy. Both methods showed that the pro-oestrous and oestrous days of the cycle were days of increased activity. Levels of hweel-running fell immediately after copulation and were low throughout pregnancy and pseudopregnancy. Except for bar-chewing, categories of behaviour scored in the home cages did not show a comparable decline. Nest-building increased during pregnancy. Sleeping was reduced on days 5 and 10 of pregnancy. The differences between the two methods of recording activity are discussed, as are the physiological bases of the changes in behaviour.
Article
Activity rhythms of pig-tailed macaques, Macaca nemestrina, were recorded under three different conditions: 1) constant illumination (LL) and constant ambient temperature; 2) light-dark (LD) cycles with 12 h of bright light and 12 h of dim light (LD 12:12) at constant ambient temperature; 3) cycles with 12 h of high (32 degrees C) and 12 h of low temperature (17 degrees C) in LL. In constant conditions the period of the free-running rhythm was positively correlated with light intensity. Ambient temperature had no systematic effect on the period in LL of 0.45 and 45 lx; when measured in 100 or 450 lx, the period was consistently longer at 32 than at 17 degrees C. Temperature cycles with a range of 15 degrees C resulted in entrainment in three adult animals, but not at all tests; two adults and a couple of young animals were never entrained. Entrainment by temperature was less accurate than that by LD. The results demonstrate that a temperature cycle can entrain the circadian activity rhythm of an homeothermic mammalian species but that it is a very weak zeitgeber compared with LD cycle.
Article
The phase and activity level of the locomotor rhythms of female golden hamsters (Mesocricetus auratus) vary in synchrony with the 4-day estrous cycle. We investigated the effects of estradiol and progesterone administration in ovariectomized hamsters to explore the interaction of these two ovarian hormones in modulating circadian locomotor rhythms. Silastic implants of estradiol shorten the period length of the rhythm, change the pattern and level of activity, and decrease the observed variance of the activity onset. Progesterone implants have no effects on the rhythm when given alone; however, when progesterone is given in combination with estradiol, all three estradiol-induced changes are blocked. These results correlate well with the observed locomotor behavior of normal female hamsters. If the levels of both estradiol and progesterone in the serum are taken into account, this correlation holds for a number of hormonal conditions including those found during the 4-day estrous cycle as well as during pregnancy and lactation. These data suggest that progesterone antagonizes the effects of estradiol in the normal animal and that the interaction of estradiol and progesterone modulates the circadian activity of female hamsters on a day-to-day basis.
Article
The circadian activity rhythms of adult female rats maintained under a light-dark cycle of 14 hr light, 10 hr dark (LD 14:10) or constant dim illumination (dim LL) were recorded during their 4 or 5 day estrous activity cycles and when they were pseudopregnant. In LD 14:10 both the phase angle difference (ψ), which defines the temporal relationship between the onsets of activity and darkness, and the period (τ) of locomotor activity differed significantly among the days of the 4 and 5 day estrous cycle. Activity-time (α) varied reliably only over the days of the 5 day estrous cycle. The period of the free-running activity rhythm in dim LL also differed significantly among the days of the estrous cycle. In both LD and dim LL the most positive ψ, shortest τ and longest α were observed on the day of estrus. Pseudopregnancy diminished the amplitude and altered the daily pattern of the estrous activity rhythm. We conclude that the periodicity of circadian activity systematically varies as a function of the stage of the estrous cycle and in a manner that cannot be solely explained by corresponding alterations in endogenous estrogen.
Article
We investigated the influence of ambient and body temperature (Ta and Tb) on circadian rhythms of gonadectomized male Siberian hamsters. Animals that entered torpor (Tb < 30 degrees C) had significantly shorter circadian periods (tau s) than did nontorpid hamsters at a Ta of 13 degrees C (24.17 +/- 0.05 vs. 24.33 +/- 0.04 h). The tau s of homeothermic hamsters were not affected by Ta change. Short-term decreases in Tb, rather than changes in Ta, appear to affect tau. Access to activity wheels inhibited expression of torpor in short daylengths and was associated with significant increases in body mass. Running wheel activity can mask or block specific short-day responses.
Article
Body temperatures were measured with a thermistor inserted through the rectum in intact and hypophysectomized male C 3 H mice, kept under standardized conditions of environmental temperature and lighting. At 1 month after hypophysectomy, temperature measurements were made on all the mice at 4-hour intervals during a 4-day period. At about 5 months after operation, measurements were made once, on separate subgroups of mice, at a 12-hour interval; this experiment was repeated 3 days later. At 1 month after hypophysectomy, the mean temperature was lower, the amplitude of daily change was smaller, and the period was slightly shorter, compared to intact controls, but there remained a significant difference between night and day mean temperatures. At about 5 months after operation, daily variations in the group mean were no longer of significant amplitude at the two times when they were measured, compared to those in intact mice.
Article
A technique for the continuous body temperature measurement of diary cows was devised using a thermistor probe and strip chart recorder. The thermogenic response elicited by progesterone administration to spayed cows (11 trials) was found to be quite marked. More immediate temperature elevations occurred when progesterone was administered intraperitoneally than when given subcutaneously. The advantage of continuous temperature recording in comparison to single daily observations was demonstrated.
Total self-regulatory functions. Harvey lectures
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