No full-text available
To read the full-text of this research,
you can request a copy directly from the author.
Abstract
Prolactin (PRL), a pituitary hormone, exerts a significant influence on reproductive functions in dogs and non-domestic canines (wolf, fox, coyote et al.). Pseudopregnancy is obligatory for all non-pregnant females in these species, which ensures their capability of caring for and even nursing a litter. This is caused by a PRL rise during the second half of pregnancy, which in the dog is quantitatively equal in pregnant and overt pseudopregnant animals; in covert pseudopregnant bitches this rise in PRL is significantly lower. Consequently, these animals do not show the enlargement of the mammary glands and their secretions, and the typical distorted behaviour seen in overtly-pseudopregnant bitches. The use of potent PRL- inhibitors, mostly dopamine agonists like bromocriptine, metergoline and cabergoline, has revealed that PRL is the luteotropic hormone from day 30 of pregnancy onward and that PRL is essential for the preparation of the mammary glands for lactation, the commencement of lactation and its maintenance, and for the maternal (and paternal) care of the litter. Hence, these PRL-inhibitors are in use for induction of abortion after mid-gestation, for the treatment of overt pseudopregnancies and to stop unwanted lactation. Male and female dogs and wolves show almost identical seasonal changes in PRL blood concentrations with peak levels before mid-year and the nadir just before the year's end. In non-domestic canines with one oestrus annually in late winter/early spring the annual PRL peak coincides with the need to care for the litter late in spring/ early in summer. Females that were pregnant or pseudopregnant are ready to nurse and take care of whelps and simultaneously, the seasonally peaking PRL blood concentrations seem to smooth over social tensions between males and ensure their essential participation in the care of the litter. In the bitch, pseudopregnancy has become an atavism and over-production of PRL causes anoestrus. Hence, PRL-inhibitors can be used for the treatment of anoestrus and for shortening the oestrous interval as well. The pseudopregnant cat does not form additional PRL, but in the pregnant cat, PRL is an essential luteotropin during the second half of pregnancy. Hence, cats can be aborted during this time period with PRL-inhibitors and these compounds are useful in order to stop lactation.
... The endocrine similarity of obligate pseudopregnancy to true pregnancy hormonally primes all females that have ovulated for maternal behavior, regardless of whether they conceived, thereby encouraging allomaternal care by non-breeding subordinate females. The hormonal similarity of pseudopregnancy and pregnancy can even cause spontaneous lactation, providing the possibility for females aside from the mother to nurse pups (Jöchle, 1997;Asa and Valdespino, 1998;van Kesteren et al., 2013). Allonursing has been reported in all Canis species except golden jackals (Lord et al., 2013) and can increase pup survival . ...
... Allonursing has been reported in all Canis species except golden jackals (Lord et al., 2013) and can increase pup survival . The potential for allo-suckling may be an adaptive function of pseudopregnancy (Macdonald, 1992;Jöchle, 1997). In gray wolves, all pack members experience seasonal peaks in prolactin coinciding with pup birth. ...
... All adult wolves, even gonadectomized individuals, experience this prolactin peak, which is identical for males and females (Kreeger et al., 1991). Prolactin is associated with parental care in other species (reviewed by Angelier and Chastel, 2009) and thus this is likely related to the parental care exhibited by all pack members, including males (Kreeger et al., 1991;Jöchle, 1997). ...
The Canidae are successful, being a widespread, abundant, speciose, and adaptable family. Several canids in particular have recently experienced rapid expansions in range and abundance, with similar situations mirrored on several continents by different species. Despite extreme behavioral diversity between and within species, monogamy is a common denominator in canid societies. In this review, we ask why canids are monogamous and how monogamy is related to their success. We begin with an overview of canid social monogamy, describing the pair bonding, paternal care, and often alloparental care that is characteristic of the family, and discuss theories on the evolution of mammalian social monogamy. We discuss why and how monogamy is maintained in canids, either voluntarily or enforced, and how ecological conditions influence either the functional advantages of monogamy or ability for enforcement and thus whether social monogamy is maintained. Social monogamy does not necessitate exclusive mating and many canids exhibit extra-pair paternity. We consider the costs and benefits of extra-pair mating for male and female canids and how ecological conditions can shift this cost/benefit balance and thus affect its prevalence. Monogamy may be responsible for many of the unusual canid reproductive characteristics through facilitating alloparental care and monogamy enforcement, and the domestic dogs' departure from monogamy supports our interpretation that it is an adaptation to resource availability. In asking whether monogamy is responsible, at least in part, for their success, we propose the monogamy as pro-cooperative hypothesis, suggesting four characteristics have contributed to canid success: (1) ecological flexibility, (2) high mobility, (3) high reproductive rates, and (4) sociality/cooperation, with the latter two being consequences of monogamy. These four interconnected traits enhance one another and it is their combination, with monogamy at its foundation enabling cooperative sociality and thereby enhanced reproduction and survival, that together comprise the formula of canid success.
... Scientific literature about prolactin normal ranges in dogs is relatively scarce. It is well documented, considering its role in lactation, that prolactin increases in pregnant and above all in lactating bitches, as well as in pseudopregnant bitches [67,68], with values ranging from 0 to around Cortisol values ranged 4.43-85.14 ng/mL (25.97 ± 20.33 ng/mL). ...
... Scientific literature about prolactin normal ranges in dogs is relatively scarce. It is well documented, considering its role in lactation, that prolactin increases in pregnant and above all in lactating bitches, as well as in pseudopregnant bitches [67,68], with values ranging from 0 to around ...
... Scientific literature about prolactin normal ranges in dogs is relatively scarce. It is well documented, considering its role in lactation, that prolactin increases in pregnant and above all in lactating bitches, as well as in pseudopregnant bitches [67,68], with values ranging from 0 to around 40 ng/mL at 10 weeks after oestrus [67,69]. As for healthy male dogs, studies carried out on intact males have found different but similar ranges [70][71][72], which can be summarised as a normal range in intact male ranging from non-detectable to 6 ng/mL [71]. ...
Prolactin has been recently regarded as a potential biomarker of both acute and chronic stress in several species. Since only few studies until now have focussed on domestic dogs, this study was aimed at evaluating whether prolactin, cortisol and stress behaviour correlated with each other in sheltered dogs. Both cortisol and prolactin analysis were performed in serum samples through a hormone-specific ELISA kit. For each dog, a stress score was calculated by summing the number of occurrences of stress-related behaviours. The presence/absence of fear during the time spent in the collection room was also scored for each individual. Results revealed a weak negative correlation between cortisol and prolactin levels. Neither of the hormones was correlated with the stress score, nor did their values seem to be influenced by showing fear in the collection room. The weak negative correlation found between cortisol and prolactin values agrees with results obtained in other studies, indicating that prolactin response might be an alternative to cortisol response. This, together with the high serum prolactin levels compared to those reported by other authors for healthy domestic dogs, may indicate that prolactin might be a good biomarker of chronic stress, and although further studies are needed to better understand the potential role of prolactin in the evaluation of canine welfare.
... Pseudopregnancy, also known as pseudocyesis is where an entire or spayed bitch shows clinical signs typical of the peri and post-partum period of pregnancy, despite the bitch not being pregnant. Pseudopregnancy can be further classified as overt, which is the clinical condition and covert, which is the normal physiological condition [1][2][3][4][5][6][7][8][9][10][11][12]. Pseudopregnancy in bitches has physiological and behavioural effects and is characterised by a range of physical and behavioural changes that commonly appear between six to eight weeks after oestrous [1,2,[11][12][13]. ...
... Pseudopregnancy in bitches has physiological and behavioural effects and is characterised by a range of physical and behavioural changes that commonly appear between six to eight weeks after oestrous [1,2,[11][12][13]. Affected dogs may experience clinical signs including enlarged mammary glands and/or milk production, weight gain, vomiting, and appetite loss [1,[3][4][5][6][7][13][14][15][16][17]. Behavioural signs consist of, but are not limited to, maternal behaviours including aggression in defence of resources, increased or reduced activity, nesting behaviour, and collecting or mothering objects [3][4][5][6][7][13][14][15][16][17][18]. ...
... Affected dogs may experience clinical signs including enlarged mammary glands and/or milk production, weight gain, vomiting, and appetite loss [1,[3][4][5][6][7][13][14][15][16][17]. Behavioural signs consist of, but are not limited to, maternal behaviours including aggression in defence of resources, increased or reduced activity, nesting behaviour, and collecting or mothering objects [3][4][5][6][7][13][14][15][16][17][18]. In some cases, the physical and behavioural signs can be marked. ...
Background
There is a dearth of literature on pseudopregnancy in the bitch, with only a few treatment-based studies published since the 1990s. Pseudopregnancy may be under-recognised in bitches and may account for a proportion of behavioural cases seen in veterinary practices including aggression. Little is known about commonly used treatments for overtly pseudopregnant bitches and it is possible that current regimes may not be prescribed for a sufficient duration to control any clinical signs including, physical and behavioural changes. To investigate current trends in diagnosis and treatment of canine pseudopregnancy, a postal survey was sent to 2000 randomly selected veterinary surgeons in UK veterinary practices. The questionnaire queried how often vets recognise cases of pseudopregnancy in spayed and entire bitches, which physical or behavioural signs are commonly recognised for diagnosis, and which management or treatment protocols are used.
Results
The response rate was 19.8% (397/2000). Ninety-six percent of veterinary surgeons reported seeing pseudopregnant bitches showing behavioural changes without any physical changes within the last 12 months. Of those behavioural changes, collecting and mothering objects was the most frequently reported behavioural sign (96%). Ninety-seven percent of vets had seen aggression in pseudopregnant bitches. Nevertheless, only 52% of vets routinely asked owners about behavioural changes during consultations. Forty-nine percent of respondents reported seeing pseudopregnancy in spayed bitches. The most commonly reported physical sign was enlarged mammary glands and/or milk production (89%). Treatment options varied (surgical, medical or none) and depended on duration and severity of physical and behavioural signs, owners’ preference, cost, concurrent disease, drug availability and previous history.
Conclusions
This is the largest epidemiological study of canine pseudopregnancy in the UK. The prevalence and severity of clinical signs in dogs with pseudopregnancy are variable and possibly under-estimated. Dogs with overt pseudopregnancy experience diverse physical and behavioural changes and information on standard treatment protocols are lacking. Although, progress on our understanding of diagnosis and treatment of pseudopregnancy in spayed and entire bitches has been made, further studies are warranted.
... The biological actions of PRL are not limited to its essential role in reproduction, but also involve regulation of the immune system, osmotic balance, angiogenesis and behaviour [1]. In the female dog, as well as in some rodent species, PRL is an essential luteotrophic hormone in the second half of pregnancy and is also involved in the display of maternal behavior234. PRL plays a promoting role in the development of human breast carcinoma, in addition to a variety of benign breast lesions5678. ...
... A prospective study already in progress will show if female dogs affected by malignant tumors in fact have increased PRL levels in addition to decreased tumorous PRLR expression. However, as PRL serum levels are extremely difficult to compare in small study populations (pulsatile PRL secretion, massive fluctuation due to season, stage of estrous cycle and individual influences) and are moreover breed-dependent [2,53545556575859, a high patient number is needed to address this question. ...
Background
Mammary tumors represent the most common neoplastic disease in female dogs. Recently, the promoting role of prolactin (PRL) in the development of human breast carcinoma has been shown. Possible proliferative, anti-apoptotic, migratory and angiogenic effects of PRL on human mammary cancer cells in vitro and in vivo were suggested. The effects of PRL are mediated by its receptor, and alterations in receptor expression are likely to play a role in tumor development. Currently, not much data is available about prolactin receptor (PRLR) expression in canine mammary tumors. To set the basis for investigations on the role of PRL in mammary tumorigenesis in this species, prolactin receptor expression was evaluated by semi-quantitative real time PCR and immunohistochemistry on 10 formalin-fixed, paraffin-embedded samples each of canine non-neoplastic mammary tissue, mammary adenomas and adenocarcinomas.
Results
The highest PRLR expression levels were found in normal mammary tissue, while adenomas, and to an even higher degree adenocarcinomas, showed a significant decrease in prolactin receptor expression. Compared to normal tissue, PRLR mRNA was reduced 2.4 fold (p = 0.0261) in adenomas and 4.8 fold (p = 0.008) in adenocarcinomas. PRLR mRNA expression was significantly lower in malignant than in benign lesions (p = 0.0165). Immunohistochemistry demonstrated PRLR expression in all three tissue types with signals mostly limited to epithelial cells.
Conclusions
Malignant transformation of mammary tissue was associated with a decline in prolactin receptor expression. Further studies are warranted to address the functional significance of this finding.
... Breeders had higher prolactin levels during the breeding season, the period of infant care, a pattern described previously for male striped mice (Schradin & Pillay 2004a). In some mammals, prolactin secretion is highest during periods of long photoperiod (Curlewis 1992;Donham et al. 1994;Jö chle 1997). In this study, the photoperiod during the breeding season ranged from 10 hours d K1 in August to 12 hours d K1 in October, while the photoperiod during the non-breeding season in March was in between with 11.5 hours d K1 ). ...
... In this study, the photoperiod during the breeding season ranged from 10 hours d K1 in August to 12 hours d K1 in October, while the photoperiod during the non-breeding season in March was in between with 11.5 hours d K1 ). The seasonal increase in prolactin levels in mammals is often discussed in relation to reproduction, which can be regulated by photoperiod (Curlewis 1992;Donham et al. 1994;Jö chle 1997). However, reproduction in male striped mice is not regulated by photoperiod ( Jackson & Bernard 1999) but by food availability ( Jackson & Bernard 2005). ...
In male fishes, birds and mammals, increased prolactin secretion is thought to play a role in species showing paternal behaviours. This hypothesis was investigated in the striped mouse (Rhabdomys pumilio). This paper compares serum prolactin levels in 71 free-living male striped mice following three different reproductive tactics: (i) paternal group-living breeders, (ii) alloparental philopatric group-living males, and (iii) roaming non-paternal solitary males. Prolactin levels of breeding males were significantly higher than that of roamers. Alloparental philopatric males had low prolactin levels, which concur with studies of cooperatively breeding mammals, but contrasts with studies of cooperatively breeding birds. Both breeding males and females showed a decrease in prolactin levels after the breeding season, but not alloparental philopatric males. Prolactin levels were correlated with neither corticosterone levels nor age. These results are in agreement with the hypothesis that prolactin is one proximate mechanism of male reproductive tactics, possibly regulating differences in male parental care.
... However, in the current study, the PRL concentration in the estrus induction group was lower 2-5 days before the LH surge than that in the spontaneous estrus group. Male and female dogs have distinct seasonal changes in PRL levels, with peaks reported before mid-year and again just before the year's end [18]. The difference in the PRL levels between the two groups before the LH surge may be due to the fact that estrus in the spontaneous estrus group was concentrated in late May, and that in the estrus induction group was in late October. ...
The effect of estrus induction by cabergoline on gonadotropin and steroid hormone responses was examined in anestrous bitches. Eleven beagles were used in the study; seven were included in the estrus induction group and four were included in the spontaneous estrus group. Cabergoline was orally administered to the estrus induction group at 5 µg/kg once daily for four weeks, or until hemorrhagic discharge was detected. The inter-estrus interval in the estrus induction group was significantly shorter than the previous estrus interval. Bitches that showed proestrus within four weeks of treatment showed increased luteinizing hormone (LH) pulse frequency and, subsequently, increased estradiol (E2) levels. Prolactin (PRL) levels declined promptly after treatment, except in one bitch that did not show proestrus during the cabergoline treatment period. There was a significant correlation between the time to proestrus induction and the reduction in PRL levels. A positive correlation was found between the LH levels two weeks after cabergoline administration and PRL reduction. This study demonstrates that an abrupt reduction in PRL is likely to be important for initiation of estrus in bitches. A reduction in PRL indirectly leads to an increase in LH pulse frequency, which regulates follicular development in bitches. However, if the period from the end of the previous estrus to the cabergoline treatment is short, it may take some time to show proestrus without increasing E2 levels, even if the LH level increases after cabergoline administration.
... Prolactin (PRL), also known as luteotropic hormone or luteotropin, is a protein that is best known for its role in enabling vixens to produce milk. Prolactin is secreted from the pituitary gland in response to eating, mating, estrogen treatment, ovulation, and nursing (Mondain-Monval et al. 1985;Jöchle 1997). Prolactin is secreted in a pulsatile fashion in between these events. ...
The purpose was to evaluate effects of feeding intensity on metabolic maintenance, reproduction and welfare in blue fox vixens. Study groups were: Group 1: heavy slimming. Ad libitum feeding during September-November, aimed to produce extremely fat animals. Heavy slimming before breeding season, aim to have animals with normal breeding body condition. Group 2: maintenance of condition. Restricted feeding 35-45% from the level of Group 1 during September-November. Natural slimming to normal breeding condition. Group 3: Rising condition. Restricted feeding 50-60% from the level of Group 1 during September-November. Aim was to produce lean animals. Rising body condition was before breeding season, aimed to have animals with normal breeding body condition. Blood samples were taken regularly throughout the study. Results showed that urea concentration varied seasonally (P<0.001). Concentrations were lowest during winter period. In Group 1, heavy slimming before mating season lowered urea concentration significantly (P<0.001). During autumn period, concentration was lowest in Group 3 because of pronounced feeding restriction. Creatinine levels were highest during summer period in all groups. Glucose concentration varied seasonally in all groups (P<0.001). Intensive feeding clearly affected on triglycerides, glucose and insulin levels (P<0.01). Growth hormone (GH) and insulin-like growth factor (IGF-1) levels were highest during autumn period. Leptin concentration was highest in December in all groups. Thereafter, it clearly declined towards summer (P<0.001). Concentration of non-esterified fatty acids (NEFA) was highest in Group 1. Prolactin levels were same in all groups until insemination. During pregnancy, levels increased similarly in groups. After whelping, prolactin levels were low (P<0.05) in Group 1 compared to other groups. Whelping result in Group 1was very low (P<0.001) compared to Groups 2 and 3. It can be concluded that feeding intensity essentially influences on hormonal levels and reproduction in blue fox vixens.
... A study using potent prolactin inhibitors, mostly dopamine agonists confirmed the role of prolactin as luteotropic hormone from day 30 of pregnancy and beyond and that it is crucial for the preparation, initiation and sustaining lactation, as well as for the activation of maternal and sexual behaviour [58]. Prolactin seems to be involved in ensuring maternal behaviour, including the preparation for delivery and the care of the litter, although it is not yet clear how it shares these effects with oxytocin [59]. ...
Mammalian parental care, in most of the cases, is given by the female, who provides food, warmth, and protection. In domestic dogs, maternal behaviour shown by the dam mainly consists of contact, nursing, grooming/licking, play, punishment, thermoregulation, and motion. Peer-reviewed literature published between 1952 and 2018 was retrieved from CAB Abstracts, PubMed, ISI Web of Knowledge, Scopus and book chapters. Keywords for this search included the following terms: behaviour, bonding, altricial, precocial, offspring, maternal , whelping, nursing, domestic dogs, female dog, aggression, puppies, anogenital licking. In this review, we reported and discussed scientific information about maternal behaviour in domestic bitches, comparing altricial vs precocial species; the importance of the bonding, grooming/licking and nursing, and their impacts on puppies' behaviour; altered maternal behaviours such as aggression, cannibalism, rejection, and also the relation between hormones and maternal care behaviours. We concluded that the level of interactions between the dam and the puppies influences the physiological, cognitive and behavioural development of the litter, and the main hormones in the bitch for inducing maternal care behaviours are estradiol, oxytocin, prolactin and progesterone.
... [4][5][6] Prolactin is essential for mammary gland development and initiation and maintenance of lactation. [7][8][9] It is a polypeptide hormone produced by lactotroph cells of the anterior pituitary gland. 10 The most important regulator of prolactin secretion is dopamine, which is produced by the hypothalamus and exerts tonic inhibition. ...
OBJECTIVE To investigate effects of metoclopramide orally administered to healthy bitches on serum prolactin and milk lactose concentrations, gross energy, and dry matter content and on puppy weight gain during early lactation.
ANIMALS 20 client-owned bitches and their 121 puppies.
PROCEDURES 10 bitches received metoclopramide (0.2 mg/kg, PO, q 6 h for 6 days; treatment group) starting 10 to 24 hours after birth of the last puppy of the litter (day 0), and 10 bitches served as the control group. Blood and milk samples from all bitches were collected on days 0, 1, 2, 4, and 6. Milk samples for days 1 and 2 and days 4 and 6 were pooled because of small volume. Puppies were weighed twice daily.
RESULTS Serum prolactin concentration increased significantly over time in both groups, and no treatment effect was detected. When day-to-day changes were analyzed, the prolactin concentration increased from day 0 to day 1 in the treatment group but not in the control group. Milk lactose concentration increased significantly and was higher in the treatment group than in the control group. Milk dry matter content was unchanged, whereas the time course for milk gross energy content differed significantly between treatment and control bitches. Puppy weight gain was not affected by metoclopramide treatment.
CONCLUSIONS AND CLINICAL RELEVANCE Oral administration of metoclopramide to healthy bitches after parturition induced a transient increase in serum prolactin concentration and stimulated milk lactose production. It is likely bitches with insufficient or delayed milk production could benefit from metoclopramide treatment.
... [4][5][6] Prolactin is essential for mammary gland development, initiation and maintenance of lactation. [7][8][9] It is a polypeptide hormone produced by the lactotroph cells of the anterior pituitary. 10 The most important regulator of PRL secretion is dopamine, which exerts a tonic inhibition from the hypothalamus. ...
Die Auswirkung der Verabreichung von Metoclopramid (MC) auf den Serumprolaktinspiegel (PRL), den Laktosegehalt (LM) sowie die Bruttoenergie (BE) und Trockenmasse der Milch (TM) wurde an 20 gesunden Zuchthündinnen verschiedener Rassen in der Frühlaktation untersucht. LM in der Milch und die Gewichtszunahme der 121 Welpen wurden bestimmt um die Wirkung auf die Milchproduktion abzuschätzen. Zehn Hunde erhielten 6 Tage (T-Gruppe) MC (0,2 mg / kg per os qid), beginnend 10-24 Stunden nach der Geburt des letzten Welpen (Tag 0). Zehn Hündinnen dienten als Kontrollen (C-Gruppe). Blut- und Milchproben wurden bei den Hündinnen am Tag 0,1,2,4 und 6 gesammelt. Die Milchproben von Tag 1 und 2 sowie von Tag 4 und 6 wurden aufgrund des geringen Volumens gepoolt. Die Welpen wurden zweimal täglich gewogen. PRL stieg in beiden Gruppen über die Zeit deutlich an. Mittels Kontrastanalyse zeigte sich ein PRL-Anstieg von Tag 0 auf Tag 1 in der T- (P = 0,050), nicht aber in der C-Gruppe. LM nahm über die Studienzeit deutlich zu und war in der T-Gruppe höher als in der C-Gruppe. Die TM war unverändert, während sich der Zeitverlauf der BE zwischen C- und T- Hunden unterschied (P = 0,006). Die Gewichtszunahme der Welpen beider Gruppen war vergleichbar. Bei gesunden Hündinnen induzierte die orale Anwendung von MC post partum eine transiente PRL-Zunahme und stimulierte die Milchlaktoseproduktion. Hunde mit unzureichender oder verzögerter Milchproduktion könnten von dieser Behandlung profitieren.
... Seal et al. [43] described a captive, barren female wolf whose endocrine profile was about the same as those of concurrently pregnant wolves, although those authors did not label the finding as pseudopregnancy . Jochle [44], indicated that pseudopregnancy is obligatory in all non-pregnant canids, including wolves. However, wolves can also show nipple development and other signs of breeding even though they had neither bred nor were pseudopregnant. ...
Information is sparse about aspects of female wolf (Canis lupus) breeding in the wild, including age of first reproduction, mean age of primiparity, generation time, and proportion of each age that breeds in any given year. We studied these subjects in 86 wolves (113 captures) in the Superior National Forest (SNF), Minnesota (MN), during 1972–2013 where wolves were legally protected for most of the period, and in 159 harvested wolves from throughout MN wolf range during 2012–2014. Breeding status of SNF wolves were assessed via nipple measurements, and wolves from throughout MN wolf range, by placental scars. In the SNF, proportions of currently breeding females (those breeding in the year sampled) ranged from 19% at age 2 to 80% at age 5, and from throughout wolf range, from 33% at age 2 to 100% at age 7. Excluding pups and yearlings, only 33% to 36% of SNF females and 58% of females from throughout MN wolf range bred in any given year. Generation time for SNF wolves was 4.3 years and for MN wolf range, 4.7 years. These findings will be useful in modeling wolf population dynamics and in wolf genetic and dog-domestication studies.
... Archives of Veterinary Science v.8, n.1, p.1-12, 2003 7 A concentração de prolactina começa a aumentar na segunda metade da gestação e esta é considerada um hormônio luteotrófico a partir deste período apenas (JOCHLE, 1997). O pico da prolactina ocorre no parto seguido por um declínio abrupto por dois dias enovo aumento, quando a lactação é estabelecida (ONCLIN e VERSTEGEN, 1997). ...
O aparelho reprodutor da cadela esta sujeito a alteracoes periodicas que estao
diretamente relacionadas ao ciclo estral. Estabelecer criterios para a identificacao desses estadios,
e do periodo de maior fertilidade da femea, e essencial para se determinar o momento ideal para
cobertura natural ou inseminacao artificial. Nos ultimos anos metodos de prevencao ou interrupcao
da gestacao tem sido descritos visando o controle populacional de caes e gatos. As medidas de
controle incluem cirurgia, terapia hormonal e, mais recentemente, controle imunologico. A
ovariohisterectomia e provavelmente o metodo de contracepcao mais adequado para animais nao
destinados a reproducao. Nos casos que envolvem a terapia hormonal como metodo contraceptivo,
a precaucao na utilizacao do medicamento no periodo mais adequado do ciclo e importante para a
diminuicao do surgimento de afeccoes uterinas e da glândula mamaria. Diante destas observacoes
essa revisao tem como objetivo abordar aspectos relacionados a fisiologia e endocrinologia
reprodutiva na cadela, enfatizando o controle reprodutivo e seus efeitos colaterais.
Reproductive endocrinology and fertility control in bitches a review
Abstract
Bitch reproductive organs of undergo periodical changes during the stages of the
estrous cycle. The establishment of features of each stage of the estrous cycle, and the period of
female higher fertility, is important for the determination of the optimal days for mating or artificial
insemination. In the last decade methods of prevention or termination of pregnancy have been
proposed for population growth control of dogs and cats This includes surgery, hormonal therapy
and, more recently, immunological control. Ovaryhysterectomy is probably the best method of
contraception for bitches not intended for breeding. In cases where hormones are used as a method
for contraception, it is important to know the precise stages of the cycle to avoid possible side effects,
like uterine or mammary gland diseases. The main concerns of the present review are the reproductive
physiology and endocrinology of the bitch and the methods for contraception and possible side
effects induced by such procedure.
... Dabei entfaltet Prolaktin seine Wirkung erst nach der Pubertät, indem es die lobuloalveoläre Entwicklung und Verzweigung der Milchgänge fördert (5,12). Bei der Hündin und einigen Nagerspezies ist Prolaktin zudem ein essentieller luteotropher Faktor in der zweiten Trächtigkeitshälfte und in die Ausprägung von maternalem Verhalten involviert (37,53,59,134). Auch bei männlichen Säugetieren ist Prolaktin an der Regulation der ...
Mammatumoren gehören zu den häufigsten neoplastischen Erkrankungen der Hündin. Hohe Prolaktinserumspiegel scheinen die kanine Mammatumorgenese zu begünstigen; Daten zur proliferationsfördernden, antiapoptotischen, migratorischen und angiogenetischen Wirkung von Prolaktin stammen vor allem aus in vitro-Studien humaner Brustkrebszellen. Über die Expression des Prolaktinrezeptors, welcher die Wirkung von Prolaktin vermittelt, liegen in der Veterinärmedizin kaum Ergebnisse vor. Zur Untersuchung der Rolle des Prolaktins in der Pathogenese kaniner Mammatumoren wurde die Prolaktinrezeptorexpression in je zehn formalin-fixierten, paraffin-eingebetteten Proben von nicht neoplastischem Gewebe, Adenomen und Adenokarzinomen mittels quantitativer Real Time PCR untersucht. Die höchste Expression wurde in normalem Mammagewebe ermittelt, in Adenomen und deutlicher noch in Adenokarzinomen war die Rezeptorexpression signifikant niedriger. Immunhistochemisch wurde die Expression des Prolaktinrezeptors ebenfalls in allen Gewebstypen, und dabei vorrangig in den epithelialen Zellen nachgewiesen. Die maligne Transformation des Gewebes spiegelte sich somit in einer Reduktion der Prolaktinrezeptorexpression wider. Diese Reduktion könnte Ausdruck eines Differenzierungsverlustes sein, ihre funktionelle Bedeutung ist unklar. Desweiteren stellt sich die Frage, inwieweit die Prolaktinwirkung an die Prolaktinrezeptorexpression gebunden ist. Diese Fragen sind Gegenstand zukünftiger Untersuchungen. = Mammary tumors are among the most common neoplastic diseases of the female dog. High serum levels of Prolactin seem to promote tumorigenesis of canine mammary tumors; Data concerning the proliferative, anti-apoptotic, migratory and angiogenetic effects of Prolactin have mainly been obtained by in-vitro-studies of human breast cancer cells. In veterinary medicine, little information is available about the expression of the prolactin receptor, which mediates the effects of Prolactin. To investigate the role of Prolactin in the pathogenesis of canine mammary tumors, Prolactin receptor expression was examined by quantitative real time PCR on 10 formalin-fixed, paraffin-embedded samples of canine normal mammary tissue, adenoma and adenocarcinoma, respectively. Highest expression levels were found in normal mammary tissue, while adenomas, and to an even higher degree adenocarcinomas, showed a significant decrease in Prolactin receptor expression. By immunohistochemistry, Prolactin receptor expression was demonstrated in each of the tissue types as well, predominantly in epithelial cells. Thus, malignant transformation of mammary tissue was associated with a decline in Prolactin receptor expression. This decline might represent a loss of differentiation, with its function not yet being understood. Furthermore, the effect of Prolactin might not necessarily be correlated with a high receptor expression rate. These questions have to be further investigated in future studies.
... Breeders had higher prolactin levels during the breeding season, the period of infant care, a pattern described previously for male striped mice (). In some mammals, prolactin secretion is highest during periods of long photoperiod (Curlewis 1992; Donham et al. 1994; Jö chle 1997). In this study, the photoperiod during the breeding season ranged fromthat prolactin is not necessary for paternal motivation (). ...
... In dogs, maintenance of pregnancy is dependent on an adequate supply of progesterone (P4), the sole source of which is the corpus luteum (CL), as the placenta is devoid of steroidogenic activity [31][32][33]. The luteal phase in pregnant and non-pregnant dogs is comparable in length and in peripheral levels of P4, estrogens and prolactin (PRL), and only relaxin concentrations are different since it is produced by the placenta [32,[34][35][36]. Therefore, other endocrine and molecular mechanisms may already be crucial early on to support survival of the embryo and to maintain a successful pregnancy. ...
Di(2-ethylhexyl) phthalate (DEHP) exposure reduces embryo implantations, increases embryonic loss, and decreases fetal body weights. However, whether it is associated with the alteration of luteal function remains unknown. Thus, our aim in this study was to explore the effect and mechanism of DEHP on luteal function in pregnant mice in vivo.
Mice were administered DEHP by gavage at 125, 250, 500 mg/kg/day from gestational days (GD) 1 to 9 or 13. Levels of serum progesterone and estradiol were measured by radioimmunoassay. The numbers and sizes of corpora lutea were calculated by ovarian histomorphology. Steroidogenic enzymes were assessed by qRT-PCR. CD31 protein was detected by immunocytochemistry, and prostaglandin F2alpha (PGF2alpha) levels were evaluated by enzyme immunoassay.
Treatment with DEHP significantly inhibited progesterone secretion in pregnant mice in a dose-dependent manner but did not inhibit estradiol production on GD 9 and 13. Treatment also showed concomitant decreases in transcript levels for key steroidogenic enzymes (CYP11A, 3β-HSD, and StAR) on GD 13. Furthermore, DEHP administration significantly reduced the numbers and sizes of corpora lutea on GD 13. No significant changes in the ratio of ovary weight vs. body weight were observed between the control group and treated animals on GD 9 and 13. In addition, treatment with DEHP significantly inhibited CD31 expression of corpora lutea, whereas plasma PGF2alpha levels in DEHP treatment groups were significantly higher compared with the control groups on GD 9 and 13.
The results show DEHP significantly inhibits luteal function of pregnant mice in vivo, with a mechanism that seems to involve the down-regulation of progesterone and steroidogenic enzymes message RNA, the decrease in CD31 expression, and the increase in PGF2alpha secretion.
... In dogs, maintenance of pregnancy is dependent on an adequate supply of progesterone (P4), the sole source of which is the corpus luteum (CL), as the placenta is devoid of steroidogenic activity313233. The luteal phase in pregnant and non-pregnant dogs is comparable in length and in peripheral levels of P4, estrogens and prolactin (PRL), and only relaxin concentrations are different since it is produced by the placenta [32,343536. Therefore, other endocrine and molecular mechanisms may already be crucial early on to support survival of the embryo and to maintain a successful pregnancy. ...
Leptin (Lep) is known for its involvement in the regulation of reproductive functions. It is important for uterine receptivity, implantation, placental growth and maternal energy homeostasis in several species, but Lep's function in the pregnant dog has not been investigated.
Pregnant bitches were ovariohysterectomized at pre-implantation, post-implantation, mid-gestation and prepartum luteolysis. Two additional groups were treated with aglepristone in mid-gestation, and ovariohysterectomized 24 or 72 h later. Lep and leptin receptor (LepR) gene expression was detected by semi-quantitative real-time PCR in pre-implantation and inter-placental uterine sections (Ut) and in utero-placental compartments (Ut/Pl). Immunohistochemistry and in situ hybridization (ISH) were performed for Lep and LepR protein and mRNA localization. Parametric one-way ANOVA, paired t-test and Wilcoxon signed-rank test were used for statistical analysis.
In the Ut/Pl, Lep expression was higher at post-implantation and prepartum luteolysis than at mid-gestation, while in the Ut, Lep mRNA levels did not change during pregnancy. LepR expression in the Ut/Pl was up-regulated at prepartum luteolysis compared to the earlier stages. In the Ut, highest LepR mRNA was found at pre- and post-implantation. LepR expression was down-regulated in the Ut/Pl compared to the Ut at post-implantation and at mid-gestation. Aglepristone treatment resulted in a decrease of Lep mRNA levels from 24 to 72 h in the Ut without concomitant changes in the Ut/Pl or in LepR levels. Lep and LepR immunoreactivities were strong in the luminal and glandular epithelium in the Ut with abundant LepR signals in the subepithelial stroma. In the Ut/Pl, fetal trophoblasts stained stronger for Lep and LepR than decidual cells, and signals for both proteins were also detected in the glandular chambers. The myometrium, blood vessel media, and sporadically also the endothelium stained for Lep and LepR. ISH showed similar signal distribution in the Ut and Ut/Pl.
Lep and LepR are differentially expressed in the canine uterus and placenta during pregnancy, and their presence in various cell types indicates paracrine/autocrine roles. The Lep signaling system may be one of the pathways involved in feto-maternal cross-talk, implantation and maintenance of pregnancy, and may have a regulatory role around parturition.
... Prostaglandins and anti-prolactinic agents are also luteolytic in carnivores. In many carnivore species pregnancy is progressively prolactin dependent and multiple doses of dopamine agonists alone or in combination with prostaglandin F 2 α will safely and effectively terminate pregnancy in the last "trimester" (Eilts, 2002;Lengwinat et al., 2001;Jöchle, 1997;Onclin and Verstegen, 1996;Onclin et al., 1995;Post and Jöchle, 1988). ...
... Cabergoline is a long-acting and potent dopamine agonist (Andreotti et al. 1995;Mantegani et al. 1999) that reduces fox reproduction rate by causing miscarriages and possibly also by reducing lactation and maternal care of the litter (Jöchle 1997;Lengwinat et al. 2001). It acts by reducing the secretion of prolactin, which in foxes has an important luteotropic effect and is essential for the maintenance of pregnancy. ...
Cabergoline is a potent inhibitor of prolactin release and a potential fertility control agent for foxes. To understand how cabergoline could behave in baits deployed for fox control, we conducted laboratory and field trials to investigate the stability of cabergoline when ( 1) in solution, ( 2) injected into a bait ( deep- fried liver and Foxoff (R)) and ( 3) exposed to a range of environmental conditions, including burial. Cabergoline, dissolved in a 1% acetic acid solution, and its carboxylic acid hydrolysis product can be assayed using high- performance liquid chromatography. When stored at 4 degrees C and at room temperature, cabergoline in solution was stable for up to 36 days. When stored under cool (<= 15 degrees C), dry conditions, cabergoline ( 800 mu g) in commercial Foxoff (R) and deep- fried ox-liver baits was stable for 28 and 7 days, respectively; stability was reduced by increases in temperature ( tested up to 40 degrees C) and humidity. Recovery of cabergoline from buried baits exposed to a range of field conditions decreased rapidly in the first week, but after 56 days remained detectable at levels of 6 - 22% of the injected amounts. This study has important implications for baiting campaigns that use cabergoline for fox control.
... 31,32 Also in male mammals, PRL is crucially involved in regulation of reproductive functions by enhancing LH effect on Leydig cells and androgen effects on accessory sex glands. 33 However, the biological actions of PRL are not limited to its role in reproduction, but it also participates in regulating numerous organ systems including immunity, angiogenesis, osmotic balance and behaviour, thereby displaying a broader range of biological functions than all other pituitary hormones together. 24 Although PRL is mainly produced by the anterior pituitary gland, it has been shown that human PRL is expressed by numerous cells and tissues: inter alia the mammary gland itself, the uterus, prostate, skin, brain, immune cells and adipocytes. ...
Mammary tumours represent the most common neoplastic disease of the female dog, and the incidence in female dogs is much higher than in women. Whereas the influence of sexual steroids on breast cancer (BC) development in dogs has been studied, very little is known about the role of prolactin (PRL). New studies show that until recently, the importance of PRL in human BC development and progression has been highly underestimated. PRL plays a role in promoting benign as well as malignant neoplastic cell growth in BC in vitro and in vivo. Sporadic publications proposed a tumour promotor role in the dog. The goal of this review is to summarize our knowledge about PRL and human BC as well as canine mammary tumourigenesis, and propose future research in this area.
... The intensity of these signs is extremely variable among bitches. Being an atavism, PSC could have had some functional importance during evolution when non-bred female wolves had to nurse other females' litters (Voith 1980;Jochle 1997). PSC is now a frequent ®nding in domestic dogs and although its exact prevalence is not known, it is estimated that it is as high as 50±75% (Johnston 1980). ...
The purpose of this article is to review the most relevant features of the physiology, clinical signs, diagnosis, treatment and prevention of canine pseudocyesis (PSC). This is a physiological syndrome, characterized by clinical signs such as: nesting, weight gain, mammary enlargement, lactation and maternal behaviour, which appears in non-pregnant bitches at the end of metaoestrus. PSC is a frequent finding in domestic dogs. Although it is generally admitted that prolactin (PRL) plays a central role in the appearance of PSC, its precise aetiophysiology is not completely understood yet. A number of clinical studies suggest that at some point of metaoestrus circulating PRL levels rise in overtly pseudopregnant bitches. Individual differences in sensitivity to PRL as well as the existence of molecular variants of canine PRL with different bioactivity versus immunoreactivity ratios may help clarify the aetiopathology of PSC. Diagnosis of PSC is based on the presence of typical clinical signs in metaoestrous non-pregnant bitches. Considering that PSC is a self limiting physiological state, mild cases usually need no treatment. Discouraging maternal behaviour and sometimes fitting Elizabethan collars to prevent licking of the mammary glands may suffice in these cases. Sex steroids (oestrogens, progestins and androgens) have been traditionally used to treat PSC but the side-effects usually outweigh the benefits of these medications. Inhibition of PRL release by ergot derivatives [bromocriptine (10-100 microg/kg per day for 10-14 days], cabergoline (5 microg/kg per day during 5-10 days), metergoline (0.2 mg/kg per day during 8-10 days) has proved to be effective for the treatment of canine PSC. Although some of these ergot derivatives present some untoward side-effects, they are transient and can usually be managed. Predisposed bitches not intended for breeding should be spayed as ovariectomy is the only permanent preventive measure.
... The decline in plasma progesterone concentration in the second half of the luteal phase may be associated with the development of overt pseudopregnancy. A mild or covert form of pseudopregnancy is present in almost all non-pregnant dogs during this part of the oestrous cycle [1] [4]. Consistent with the concept that a rapid lowering of plasma progesterone concentration plays a pivotal role, overt pseudopregnancy often occurs after ovariectomy performed during the luteal phase. ...
A decline in circulating progesterone concentration plays an important role in the ethiopathogenesis of pseudopregnancy in the bitch. Because growth hormone (GH) and prolactin (PRL) are essential for normal mammogenesis and the secretion of these hormones is influenced by changes in the circulating progesterone concentration, the purpose of this study was to investigate the effects of mid-luteal phase ovariectomy on the 6-h pulsatile plasma profiles of GH and PRL and the basal plasma concentrations of GH, PRL, and insulin-like growth factor-I (IGF-I) in six beagle bitches.
... Prolactin is considered a luteotropic www.journals.elsevierhealth.com/periodicals/the Theriogenology 66 (2006) 145-150 hormone [5]. Administration of a prolactin-inhibiting drug, cabergoline, in the latter half of gestation caused a decrease in serum progesterone concentration and from 88% to 100% of treated queens subsequently aborted [4,6], suggesting that corpora lutea are the primary source of progesterone during pregnancy in cats. ...
Average gestation length in domestic cats is 65.6 days, with a range of 52-74 days. Average reported litter size is 4.0 kittens per litter; litter size is not correlated with number of matings in a given estrus. Superfecundation is common in domestic cats; superfetation never has been definitively proven to occur. Eclampsia may occur during pregnancy in queens, with non-specific clinical signs. Ectopic pregnancy and uterine torsion have been reported. Pregnancy loss may be due to infectious causes, including bacteria, viruses or protozoa, or non-infectious causes, such as hypoluteoidism and chromosome errors.
... Plasma Prl concentrations, a hormone related to reproduction and also a marker of animal stress, did not differ either between sexes or species. It is not known whether cats have a rhythm of Prl secretion (Jochle, 1997). The greatest daily variations in plasma Prl concentration occur in response to photoperiod with the highest levels occurring at night as is the case for melatonin (Leyva et al., 1984Leyva et al., , 1989a,b). ...
Many neotropical felines are threatened with extinction and information on their physiology is required to assist in conservation. Their reproduction in captivity is poor, particularly for the smaller species. Several factors may be responsible, but stress is probably the most important. We assayed cortisol, LH, FSH, prolactin, testosterone, estradiol, and progesterone in single blood samples obtained under sedation from seven neotropical species and, for comparison, in stressed and unstressed domestic cats. Cortisol was also assayed in serial blood samples obtained after ACTH administration in Leopardus tigrinus, L. wiedi and domestic cats. While, in general, the results were fairly consistent, there were some statistically significant differences between species that were large enough to be of practical importance.
Canine mammary cancer (CMC) is one of the most common neoplasms in intact females in comparison to other species. Several risk factors have been identified, including breed, genetic predisposition, age, reproductive history, hormonal influence, diet, and body condition, in addition to previous lesions to the mammary gland, such as mammary atypical hyperplasia. An understanding of the genetic markers for the disease and a clinical approach are important for establishing a specific therapy that can allow adequate patient survivorship. Overexpression of the HER-2 gene in canines and humans is associated with a poor clinical prognosis, mainly short survivorship, although the clinical relationship is not clear. The incidence of HER-2 in female dogs can range from 29.7% to 38%. However, overexpression of HER-2 is not necessarily associated with malignancy processes of the mammary tissue, although it participates in cellular proliferation. Finally, canines remain one of the most important models for comparative oncology with humans due to the great similarity in the spontaneous presentation and development of cancer, and in the high homology in the amino acid sequence.
The self-domestication hypothesis suggests that, like mammalian domesticates, humans have gone through a process of selection against aggression – a process that in the case of humans was self-induced. Here, we extend previous proposals and suggest that what underlies human social evolution is selection for socially mediated emotional control and plasticity. In the first part of the paper we highlight general features of human social evolution, which, we argue, is more similar to that of other social mammals than to that of mammalian domesticates and is therefore incompatible with the notion of human self-domestication. In the second part, we discuss the unique aspects of human evolution and propose that emotional control and social motivation in humans evolved during two major, partially overlapping stages. The first stage, which followed the emergence of mimetic communication, the beginnings of musical engagement, and mimesis-related cognition, required socially mediated emotional plasticity and was accompanied by new social emotions. The second stage followed the emergence of language, when individuals began to instruct the imagination of their interlocutors, and to rely even more extensively on emotional plasticity and culturally learned emotional control. This account further illustrates the significant differences between humans and domesticates, thus challenging the notion of human self-domestication.
The proportion by age class of wild Canis lupus (Gray Wolf) females that reproduce in any given year remains unclear; thus, we evaluated the applicability to our long-term (1972–2013) data set of the Mech et al. (1993) formula that categorizes female Gray Wolf breeding status by nipple size and time of year. We used the formula to classify Gray Wolves from 68 capture events into 4 categories (yearling, adult non-breeder, former breeder, current breeder). To address issues with small sample size and variance, we created an ambiguity index to allow some Gray Wolves to be classed into 2 categories. We classified 20 nipple measurements ambiguously: 16 current or former breeder, 3 former or adult non-breeder, and 1 yearling or adult non-breeder. The formula unambiguously classified 48 (71%) of the nipple measurements; based on supplemental field evidence, at least 5 (10%) of these were incorrect. When used in conjunction with an ambiguity index we developed and with corrections made for classifications involving very large nipples, and supplemented
with available field evidence, the Mech et al. (1993) formula provided reasonably reliable classification of breeding status in wild female Gray Wolves.
SUMMARY The domestic cat can be defined as a seasonal poliestrous female. During mating the physical stimulus produce the release of LH and ovulation, which occur during the first 50 hours post mating. The fertilization of oocytes takes place inside the oviduct during the 30 hours post ovulation. The embryos transport on the oviduct takes about 132 hours and when embryos reach the uterus they are already a compacted morulae. After this, the blastocyst migrates to both uterine horns for a period of 80 hours aproximately until implantation ocurrs 12 to 13 days after mating. During the preimplantation period, there is a significant increase in blood progesterone and also in LH lutheal receptors. From the second half of gestation, the production of progesterone decrease and prolactin secretion increase. Thus it is thought that the later would be the main luteotrophic agent in the cat. Also during the second half of gestation the secretion of relaxin increase. The production and function of progesterone during late gestation is controversial. It has been shown that placenta of cats has a steroidogenic function and that it is also to produce progesterone.
Wild Canis species possess a unique suite of reproductive traits including social monogamy, copulatory lock/tie, and biparental care. Females are seasonally monestrous and experience an obligatory pseudopregnancy after spontaneous ovulation. While these characteristics have been ascribed to coyotes, an integrated profile of behavior and physiology has not yet been described. In this study, temporal correlations between steroid hormone levels and socio-sexual mating behaviors were documented, as were changes in vaginal epithelium. Pseudopregnancy was compared to pregnancy by contrasting hormone (progesterone, estradiol, prolactin and relaxin) profiles of unmated females to patterns obtained in alternate years when they bred. Meanwhile, social interactions between pseudopregnant females and their mates appeared similar to pregnant coyotes, suggesting a proximate role of pseudopregnancy in pair-bond enforcement. Finally, out-of-season stimulation of ovarian hormones and estrous behaviors suggested that reproductive seasonality of the coyote may possess some degree of plasticity, providing an adaptive response mechanism to environmental change.
Concentrations of progesterone, prolactin and relaxin in serum at predetermined intervals after ovulation (day 0) in non-pregnant and pregnant normocyclic Beagles were assayed and results compared with those observed in German Shepherd dogs (GSD) in a previous study. The goal was to determine possible reproductive hormone specificities related to the GSD breed. Furthermore, the effects of medroxyprogesterone acetate (MPA)-treatment in non-pregnant Beagles and of progesterone supplementation in pregnant Beagles on the hormone concentrations were examined. Mean concentrations of progesterone and prolactin were not different in the non-pregnant Beagles compared with those seen in non-pregnant GSD, except at days 50-60, when progesterone concentrations were found to be higher in Beagles (p < 0.05). Mean progesterone concentrations in pregnant Beagles at days 50-60 after ovulation (day 0) were higher (p < 0.05) than in GSD at that time, but not at earlier time periods. Prolactin concentrations were higher (p < 0.05) in Beagles throughout pregnancy compared with those in the GSD. Mean relaxin concentrations were numerically but not significantly lower in GSD than in Beagles throughout pregnancy. A 10-day oral MPA treatment did not affect progesterone or prolactin secretion in normocyclic non-pregnant Beagles. Medroxyprogesterone acetate serum concentrations were approximately 3.9 ng/ml during treatment and decreased to 0.42 and 0.021 ng/ml within 5 and 15 days after end of treatment, respectively. Intramuscular progesterone supplementation from days 30 to 40 in pregnant Beagles resulted in higher concentrations of progesterone in the 36- to 45-day time periods; prolactin and relaxin concentrations were not significantly affected during or after treatment compared with administration of placebo. The results suggest a tendency towards deficient luteal function in the short-cycle GSD bitches previously studied, which in pregnancy may reflect the observed decreased prolactin concentrations; the possibility that GSD relaxin secretion is deficiency required needs further study. As oral treatment with MPA did not affect progesterone and prolactin release, it may be useful for studying luteal function in pregnant bitches with suspected hypoluteoidism.
Accurate detection of pregnancy is a useful tool in zoo management and husbandry, conservation breeding programs and research settings. Our study evaluated the ability of a commercial relaxin hormone assay used in domestic dogs (ReproCHEK(TM)) to accurately detect pregnancy through plasma analysis in two wolf and two fox species. The relaxin assay detected all of the pregnancies greater than 25 days gestation for island foxes, fennec foxes, gray wolves, and Mexican gray wolves. For island foxes, three negative relaxin results were attributed to using the test earlier postconception than manufacturer recommendation (before day 20). Five other negative results were found for females estimated at 15-25 days gestation, spanning the early and intermediate period (21-30 days gestation) when relaxin may be detected but less reliably. There were no false-positive results in nonmated negative control animals. Relaxin assay results were highly correlated with ultrasound results and the intra-assay replicate agreement was 100%. Our results show that the ReproCHEK(TM) commercial relaxin assay is a minimally invasive and reliable method for pregnancy detection in these wild species when used after 25 days gestation and might be applied to other canids as well. Furthermore, this assay is easy to run and requires no specialized equipment, making it extremely useful for zoo and field research applications. Zoo Biol 27:406-413, 2008. (c) 2008 Wiley-Liss, Inc.
The use of progestins to suppress endogenous testosterone production to reduce agonistic behavior and prevent semen production was studied in gerenuk. Five male gerenuk (20 months to 3 years of age), housed as a bachelor group, were treated with 3 monthly injections of medroxyprogesterone acetate (MPA; 2.5-20 mg/kg), followed by a melengestrol acetate implant (MGA; 0.3 g/kg) for 2 months. Blood samples collected monthly were assayed for serum testosterone and cortisol using enzyme-linked immunoassays. Quantitative behavioral data were collected for 30 min 3/week starting 1 month before treatment. Body weight, testes volume, and semen traits were measured before treatment, after MPA treatment, and after MGA treatment. Results showed lower (P<0.05) mean serum testosterone concentrations after MPA (4.34 pg/ml) and MGA (5.02 pg/ml) treatment compared to pre-treatment values (65.9 pg/ml) in four of five gerenuk. The remaining sub-adult gerenuk had low testosterone initially (4.9 pg/ml) that did not decrease further with treatment (1.4 and 7.8 pg/ml for MPA and MGA, respectively). Mean serum cortisol concentrations decreased markedly after treatment with MPA (6.0+/-3.7 ng/ml) and MGA (0.8+/-0.3 ng/ml). Cortisol concentrations were regained rapidly post-treatment (42.8+/-4.8 ng/ml) and were not significantly different from the pre-treatment value (60.6+/-12.6 ng/ml; P>0.05). The mean incidence of combined aggressive/dominant behaviors (horning, sparring, supplanting, threat) was not different before and after treatment. Body weight, total numbers of spermatozoa produced per ejaculate, percent motility, and percent normal spermatozoa declined maximally 8 months after treatment. Mean testes volume decreased (P<0.05) after MGA treatment (10.53 cm(3)vs. 11.96 cm(3) pre-treatment). Elevated hepatic enzymes and bile acids were seen in three of five animals after progestin treatment and anorexia was noted in two males after MGA implant removal, however two of three males had elevated liver enzymes before progestin treatment began. Results show that reducing serum testosterone concentration does not seem to modify agonistic behavior in bachelor gerenuk groups. Zoo Biol 26:245-257, 2007. (c) 2007 Wiley-Liss, Inc.
The Arctic Fox Alopex lagopus semenovi population on Mednyi Island is completely isolated and subsists largely by scavenging on seabird colonies, which have remained abundant and spatio-temporally predictable for many years. We compared population data at the beginning of 1976/1978 and some time after 1994-2005, finding an 85% decline in fox numbers due to disease, to assess the effect of population size on social structure. A total of 81 groups of known size and composition was observed during this 29-year period. Overall, helpers (usually non-lactating yearling females) occurred in 25.7% of groups, and in 32.4% of groups there were two or three lactating females. Female engagement in alloparental behaviour decreased, but not statistically significantly, after the decline in population density. Total food availability was apparently constant throughout the study period, and therefore, the amount available per individual was much higher later in the study. Both communally nursing females and helpers brought food and helped to guard the litter. However, the benefits of communal rearing were unclear. While cubs were left without guards significantly more rarely in the groups with an additional adult, the number of cubs weaned per lactating female was greater in groups with one (3.93 +/- 1.60), as opposed to two or three (3.06 +/- 0.92), lactating females. Survival of cubs to 1 year of age in the groups with two lactating females and/or with helpers was lower than that in the families with one lactating female without helpers (22.2% vs 32.2%). Fewer second-generation litters were born to foxes produced by composite families than to those produced by pairs. Reproductive adults producing by pairs had, on average, 1.23 (+/-1.72) second-generation litters. In groups that initially included additional adults, the average number of second-generation litters per reproductive female was 0.21 (+/-0.49) and 0.46 (+/-0.81) litters per male. Thus, according to three measures, increased group size had no apparent positive impact on reproductive success. The increased parental investment and enhanced guarding of the cubs in the larger families could be beneficial under conditions of high population density and a saturated biotope to which the island fox population was presumably adapted before the population crash in the late 1970s.
Prolactin has long been known to play a significant role in maternal care. When behavioral endocrinologists began to examine the endocrinology of fatherhood, prolactin was also found to be connected with paternal care in fish, birds, and mammals including primates.
Radioimmunoassays for canine FSH and prolactin were developed and used to quantitate these hormones during proestrus, estrus, pregnancy and nonlactational pseudopregnancy of the bitch. The assay for FSH consists of a rabbit anti-ovine FSH serum, radioiodinated human FSH and NIH-FSH-S4 as standard. Inhibition curves produced by the standard, crude extracts of canine pituitary glands and various canine sera were parallel. FSH in extracts of canine pituitary glands could be quantitatively recovered when added to canine serum. The material in pituitary extracts which inhibited binding of radioiodinated human FSH to the antibody migrated on polyacrylamide electrophoresis gels coincident with radioiodinated human FSH. After injection of GNRH, levels of FSH in serum increased about 50% in 15 min, whereas injections of CB-154 or TRH did not influence levels of FSH. Sensitivity of the FSH assay is 580 pg which is adequate to quantify the concentration of FSH in 200 μl or less of canine serum. The prolactin assay consists of guinea pig anti-porcine prolactin serum, radioiodinated ovine prolactin serum, radioiodinated ovine prolactin and NIH-P-S8 as standard. Sera from dogs during various reproductive states produced inhibition curves which were parallel to the standard curve. The inhibiting material in this assay migrated like radioiodinated ovine prolactin following electrophoresis. Prolactin in extracts of canine pituitary glands was quantitatively recovered after addition to canine serum. Levels of prolactin in serum of male dogs were elevated approximately 5-fold within 20 min after injection of TRH, whereas injection of CB-154 decreased levels of prolactin by 75% 3 h after injection. Injection of GNRH did not affect serum levels of prolactin. Sensitivity of the prolactin assay was 9 pg of NIH-P-S8 which allowed estimation of prolactin concentrations in 200 μ1 or less of canine sera. During the reproductive cycle, levels of FSH were lowest during proestrus (56.3±8.7 ng/ml) and increased to 167.6 ± 36.9 ng/ml on the first day of estrus. Levels of FSH declined by Day 6 postestrus(69.2 ± 14.7 ng/ml) then increased to 254.8±27.8 ng/ml in pregnant bitches and 107.5±22.2 ng/ml in pseudopregnant bitches on Days 55-58. Mean levels of prolactin in serum appeared to exhibit cycles of 3-4 days duration and were highest on the days immediately preceding parturition. Levels of prolactin did not differ significantly between pregnant and pseudopregnant bitches.
Concurrent changes in serum progesterone, cortisol and prolactin associated with the prepartum period and lactation of 6 suckling and 1 nonsuckling Beagle bitches were determined by radioimmunoassay. Progesterone in each bitch fell sharply prior to parturition and remained low during lactation. Mean progesterone at approximately 120, 36, 20 and 10 h prepartum was 4.5 ± 0.6, 3.1 ± 0.4, 1.2 ± 0.4 and 0.6 ± 0.1 ng/ml, respectively. In 6 of 7 bitches, serum cortisol was elevated above mean prepartum levels (23 ± 1 ng/ml) during the day prior to the onset of parturition, reached peak levels of 63 ± 7 ng/ml at 8-24 h prepartum and fell to 19 ± 4 ng/ml at 8-12 h postpartum. Mean cortisol remained between 22 ± 1 and 27 ± 5 ng/ml during lactation and weaning. During the last week of pregnancy, serum prolactin levels (14-97 ng/ml) were variable within (50 ± 2 to 33 ± 8 ng/ml) and among (25 ± 2 to 80 ± 9 ng/ml) bitches and averaged 40 ± 7 ng/ml. In each bitch, prolactin increased by 195 ± 29% during the 16-56 h prepartum and reach peak levels (117 ± 24 ng/ml) at 8-32 (21 ± 3)h prepartum in 6 bitches and at 24 h postpartum in the remaining bitch. By 36 h after these peaks, prolactin levels were reduced to 37 ± 8 ng/ml before again increasing in response to suckling. Mean prolactin increased during the first week of lactation, peaked at 86 ± 19 ng/ml at 1.5 weeks of lactation, fell slowly to 43 ± 6 ng/ml at 5 weeks, shortly before weaning and then fell abruptly to 13 ± 2 ng/ml following weaning. The hormone changes observed were similar to those reported for several other species and suggest that the bitch may be a useful model for the study of maternal endocrine adjustments.
Beagle bitches were treated with equine anti-LH serum (ALHS) or the dopamine agonist bromocriptine at selected times during the 2-month luteal phase of the ovarian cycle or pregnancy. After a single injection of ALHS (10 ml, i.m.) at Day 42 of pregnancy (N = 2) or the ovarian cycle (N = 3), progesterone was reduced (P less than 0.05) to 7-24% of preinjection values within 1-2 days, and by 4-8 days returned to levels not different from those in control bitches treated with normal horse serum. Injections of bromocriptine (0.1 mg/kg, i.m.) daily for 6 days caused abrupt declines in progesterone which lasted 6-8 days in bitches treated at Day 8 or 22 of pregnancy (N = 5). In bitches treated at Day 42 of pregnancy (N = 3) or in non-pregnant cycles (N = 4) the bromocriptine treatment caused declines (P less than 0.05) in progesterone which were permanent, extensive (less than 2 ng/ml), and therefore abortive. The declines in progesterone in response to immunoneutralization of LH and to prolactin-lowering doses of a dopamine agonist demonstrate that normal luteal function in dogs requires both LH and prolactin.
A heterologous radioimmunoassay system developed for the rabbit and suitable for a wide range of mammalian species has been shown to measure prolactin in the plasma of the blue fox. Evaluation of prolactin levels throughout the year showed the concentrations displayed a circannual rhythm with the highest values occurring in May and June. Prolactin concentrations remained low (approximately 2.5 ng/ml plasma) from July until April with no consistent changes found around oestrus (March-April). In 8 pregnant females, the prolactin increase in late April and May coincided with the last part of gestation and lactation: concentrations (mean +/- s.e.m.) increased to 6.3 +/- 0.6 ng/ml at mid-gestation, 9.7 +/- 2.1 ng/ml at the end of gestation and 26.7 +/- 5.0 ng/ml during lactation. In 10 non-pregnant animals, the mean +/- s.e.m. values were 7.2 +/- 1.2 ng/ml in April, 8.8 +/- 2.2 ng/ml in May and 9.8 +/- 1.3 ng/ml in June. The prolactin profile in 4 ovariectomized females was similar to that observed in non-pregnant animals, but the plasma values tended to be lower during the reproductive season (April-June). In intact females, the only large LH peak (average 28 ng/ml) was observed around oestrus. During pro-oestrus, baseline LH levels were interrupted by elevations of 3.1-10.4 ng/ml. During the rest of the year, basal levels were less than 3 ng/ml. In ovariectomized females, LH concentrations increased within 2 days of ovariectomy and remained high (35-55 ng/ml) at all times of year.
In some mammals, both sexes exhibit a high degree of parental behaviour. This is the case in many primates which form pair bonds, such as marmosets, tamarins, owl monkeys and siamangs1-4. It is not known if any endocrine changes occur in male mammals which show parental behaviour. We report here that in male common marmosets carrying their twin offspring, plasma prolactin levels are five times higher, on average, than in males without infants. There are, however, no consistent differences in levels of plasma testosterone. Increases in prolactin are most pronounced during periods when males (rather than other group members) are carrying their offspring. This suggests that physical contact may be important in producing the effects. Although prolactin has been implicated in the control of maternal behaviour in avian and mammalian species5-8 this is the first demonstration that prolactin is elevated during parental behaviour in a male mammal.
Concentrations of estradiol, progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin in serum from 6 bitches bled daily for at least 45 days before the onset of proestrus, during proestrus and estrus were determined by radioimmunoassay. Mean concentrations of estradiol in serum were high early in the sampling period (20 to 46 pg/ml) and appeared to decrease prior to the onset of proestrus (8 to 19 pg/ml). There were sporadic increases in serum concentrations of LH throughout the sampling period in each bitch. Five of the 6 bitches sampled had increased serum concentrations of LH following the low mean concentration of estradiol just before the onset of proestrus. Mean concentrations of FSH were highest during anestrus (240 to 294 ng/ml) and near the time of the preovulatory surge of LH (297 ng/ml) and were lowest during proestrus (131 to 200 ng/ml). The mean concentration of progesterone for the 6 bitches remained at less than 1.0 ng/ml throughout late anestrus, but increased to greater than 1.0 ng/ml the day of the maximum mean concentration of LH (preovulatory LH surge). Mean concentrations of prolactin were variable throughout the sampling period and demonstrated no consistent pattern among bitches. The results of the current investigation suggest that neither the canine ovary nor pituitary are quiescent during anestrus. The bitch appears to have sufficient FSH present during anestrus for follicular growth. Serum concentrations of LH appear to increase prior to the onset of proestrus when concentrations of estradiol are lowest, possibly inducing a new follicular phase. Progesterone and prolactin do not appear to be involved in the termination of anestrus in the bitch.
The endocrine basis of reproductive failure in red fox vixens was examined over two breeding seasons in a total of 11 animals. Weekly blood samples were assayed for progesterone, prolactin, LH and cortisol. Vaginal smears taken every 2 days over the oestrous period indicated that all vixens had mated. Vixens that successfully gave birth to a litter of cubs demonstrated significantly higher plasma progesterone and prolactin concentrations but significantly lower cortisol concentrations than did females that had ovulated, but then failed to whelp. There were no significant differences in plasma LH concentrations. These data suggest that reproductive losses could result from lowered plasma progesterone concentrations, possibly resulting from inadequate luteotrophic support by prolactin. A stress-induced mechanism of reproductive failure is implicated and is discussed in relation to social suppression of reproduction.
The sensitivity of the pituitary to GnRH in early and late anoestrus and the indirect response of the ovary were investigated in six adult beagle bitches. Plasma concentrations of LH and oestradiol were determined after i.v. injection of graded doses of GnRH (0, 0.01, 0.1, 1, 10 and 100 micrograms kg-1). The responses were measured by the LH and oestradiol concentration profiles over time. The responses of LH and oestradiol were significantly dose dependent (P = 0.002 and P < 0.001, respectively). The responses of LH and oestradiol were significantly higher (P = 0.02 and P = 0.001, respectively) in late anoestrus than in early anoestrus. The responses of LH and the responses of oestradiol were positively correlated (r = 0.97, P = 0.001). It is concluded that during the course of anoestrus in the bitch pituitary sensitivity to GnRH increases while the ovary responds accordingly.
Cooperative breeding refers to a social system in which individuals other than the parents provide care for the offspring. Since individuals delay breeding and invest in the offspring of others, cooperative breeding poses a challenge to a Darwinian explanation of the evolution of social behaviour. The contributors to this book explore the evolutionary, ecological, behavioural and physiological basis of cooperative breeding in mammals. The book contains a collection of chapters by the leading researchers in the field, and it is dedicated exclusively to the study of mammalian cooperative breeding. It will appeal to zoologists, ecologists, evolutionary biologists, and to those interested in animal behaviour.
Radioimmunoassays for canine FSH and prolactin were developed and used to quantitate these hormones during proestrus, estrus, pregnancy and nonlactational pseudopregnancy of the bitch. The assay for FSH consists of a rabbit anti-ovine FSH serum, radioiodinated human FSH and NIH-FSH-S4 as standard. Inhibition curves produced by the standard, crude extracts of canine pituitary glands and various canine sera were parallel. FSH in extracts of canine pituitary glands could be quantitatively recovered when added to canine serum. The material in pituitary extracts which inhibited binding of radioiodinated human FSH to the antibody migrated on polyacrylamide electrophoresis gels coincident with radioiodinated human FSH. After injection of GNRH, levels of FSH in serum increased about 50% in 15 min, whereas injections of CB-154 or TRH did not influence levels of FSH. Sensitivity of the FSH assay is 580 pg which is adequate to quantify the concentration of FSH in 200 µl or less of canine serum. The prolactin assay consists of a guinea pig anti-porcine prolactin serum, radioiodinated ovine prolactin and NIH-P-S8 as standard. Sera from dogs during various reproductive states produced inhibition curves which were parallel to the standard curve. The inhibiting material in this assay migrated like radioiodinated ovine prolactin following electrophoresis. Prolactin in extracts of canine pituitary glands was quantitatively recovered after addition to canine serum. Levels of prolactin in serum of male dogs were elevated approximately 5-fold within 20 min after injection of TRH. whereas injection of CB-154 decreased levels of prolactin by 75% 3 h after injection. Injection of GNRH did not affect serum levels of prolactin. Sensitivity of the prolactin assay was 9 pg of NIH-P-S8 which allowed estimation of prolactin concentrations in 200 µl or less of canine sera. During the reproductive cycle, levels of FSH were lowest during proestrus (56.3±8.7 ng/ml) and increased to 167.6±36.9 ng/ml on the first day of estrus. Levels of FSH declined by Day 6 postestrus (69.2± 14.7 ng/ml) then increased to 254.8±27.8 ng/ml in pregnant bitches and 107.5±22.2 ng/ml in pseudopregnant bitches on Days 55-58. Mean levels of prolactin in serum appeared to exhibit cycles of 3-4 days duration and were highest on the days immediately preceding parturition. Levels of prolactin did not differ significantly between pregnant and pseudopregnant bitches.
Concurrent changes in serum progesterone, cortisol and prolactin associated with the prepartum period and lactation of 6 suckling and 1 nonsuckling Beagle bitches were determined by radioimmunoassay. Progesterone in each bitch fell sharply prior to parturition and remained low during lactation. Mean progesterone at approximately 120, 36, 20 and 10 h prepartum was 4.5 ± 0.6, 3.1 ± 0.4, 1.2 ± 0.4 and 0.6 ± 0.1 ng/ml, respectively. In 6 of 7 bitches, serum cortisol was elevated above mean prepartum levels (23 ± 1 ng/ml) during the day prior to the onset of parturition, reached peak levels of 63 ± 7 ng/ml at 8-24 h prepartum and fell to 19 ± 4 ng/ml at 8-12 h postpartum. Mean cortisol remained between 22 ± 1 and 27 ± 5 ng/ml during lactation and weaning. During the last week of pregnancy, serum prolactin levels (14-97 ng/ml) were variable within (50 ± 2 to 33 ± 8 ng/ml) and among (25 ± 2 to 80 ± 9 ng/ml) bitches and averaged 40 ± 7 ng/ml. In each bitch, prolactin increased by 195 ± 29% during the 16-56 h prepartum and reach peak levels (117 ± 24 ng/ml) at 8-32 (21 ± 3) h prepartum in 6 bitches and at 24 h postpartum in the remaining bitch. By 36 h after these peaks, prolactin levels were reduced to 37 ± 8 ng/ml before again increasing in response to suckling. Mean prolactin increased during the first week of lactation, peaked at 86 ± 19 ng/ml at 1.5 weeks of lactation, fell slowly to 43 ± 6 ng/ml at 5 weeks, shortly before weaning and then fell abruptly to 13 ± 2 ng/ml following weaning. The hormone changes observed were similar to those reported for several other species and suggest that the bitch may be a useful model for the study of maternal endocrine adjustments.
Prolactin (PrI) secretion patterns were investigated during pregnancy, parturition, lactation and the weaning period of 8 cats by means of a heterologous radioimmunoassay (RIA) using canine PrI antisera and canine reference standards (NIAMDD). Prl concnetrations began to increase during the sixth week of pregnancy (gestation period, 9.5 weeks) and were significantly higher from the seventh week through the last week of pregnancy (�-31.2 ± 5.1 ng/ml) compared to the first 5 weeks (X.7.0 ± 0.3 ng/ml). PrI values averaged 43.5 ± 4.5 ng/ml for the last 3 days of gestation. In the 5 animals that lactated for 6 weeks postpartum, PrI levels remained high (40.6 ± 7.2 ng/ml) for the first 4 weeks postpartum. Pri concentrations averaged 27.8 ± 3.1 ng/ml during the last 2 weeks of lactation, a significant decline from the previous 4 weeks (P<0.05). Following weaning, Prl concentrations decreased to approximately 15 ng/ml during the first week with basal levels obtained by the end of the second week. In the 3 nonlactating animals, basal levels of PrI were achieved by 1, 3, and 10 days postpartum. During pseudopregnancy (the period of luteal production of progesterone, nonpregnant state) there were no significant changes in Pr! concentrations observed with a blood sampling regimen of one daily morning sample (X-7.3 ± 0.6 ug/mI). From this study, the following conclusions were drawn: 1) It is possible to measure PrI levels in the cat with the canine Prl system. 2) Prl levels are elevated in the last one-third of pregnancy, presumably for the induction of mammary gland growth and lactogenesis. 3) With the suckling stimulus, PrI levels are elevated during the 6-week lactation period; however, during the last 2 weeks of lactation, PrI levels decline significantly to about one-half of the immediate postpartum levels. Following weaning, PrI concentrations return to basal levels within 1 to 2 weeks. 4) Coitusinduced pseudopregnancy (without lactation) has no significant effect on PrI levels.
In den vorliegenden Untersuchungen wurde geprüft, ob und unter welchen Bedingungen pränatale und/oder galaktogene Infektionen mit Ancylostoma caninum beim Hund vorkommen, wie der Ablauf galaktogener Infektionen gestaltet ist, in welchen Geweben histotrope Larven von Ancylostoma caninum beim Hund lokalisiert sind und ob es bei impatent infizierten, laktierenden Hündinnen möglich ist, eine Larvenausscheidung mit der Milch experimentell zu induzieren. Die Versuche erfolgten an helminthenfrei aufgezogenen Beagles, die einheitlich mit 20 000 dritten Larven von Ancylostoma caninum einmalig per os oder perkutan infiziert und z. T. später an 10 aufeinanderfolgenden Tagen mit je 2000 dritten Larven reinfiziert worden waren. Es wurden u. a. folgende Ergebnisse erzielt:
SYNOPSIS. Melatonin, a hormone of the pineal gland, exerts multiple effects upon the brain-pituitary axis of vertebrates. Among mammals, the best documented physiological roles of melatonin involve the photoperiodic induction of reproductive and other seasonal adjustments. Daylength regulates the effects of gonadal steroids upon gonadotropin secretion and sexual behavior as well as the frequency of a neural generator of GnRH pulses. In hamsters, these effects are paralleled by changes in GnRH, AVP and beta-endorphin immunoreactivity, and in opiate receptor density in the medial amygdala. Autoradiographic studies indicate a high concentration of 2[ 125I]-iodomelatonin binding sites in the suprachiasmatic nuclei of some photoperiodic mammals but not in others. In contrast, such binding sites have been found in the pars tuberalis of all seasonally breeding mammals studied to date.
SYNOPSIS. There is mounting evidence that prolactin influences reproductive function in several vertebrate species via direct action on the central nervous system. In most instances, however, the basic properties of these prolactin-induced alterations in brain function, the neurochemical mechanisms underlying these effects, and the identity of the prolactinlike molecules that might normally promote these changes have yet to be adequately characterized. Several properties of the prolactin-brain relationship that have emerged from our work in the ring dove (Streptopelia risoria) are described in this paper and discussed in relation to similar work in other species. Receptor binding studies using radiolabelled mammalian prolactin preparations consistently indicate the existence of saturable, high affinity binding sites for prolactin in the brains of several vertebrate species. The apparent concentration of these sites in the diencephalon is corroborated by recent mapping studies in rabbits, ring doves, and three song birds in which in vitro autoradiography and densitometry was employed. Nevertheless, direct comparisons among the three songbird species suggest some differences in the precise distribution and/or concentration of prolactin binding sites within the preoptic-hypothalamiccontinuum that may relate to species differences in the display of prolactin- related incubation behavior and parental activities. Although definitive evidence is currently lacking, it would appear that blood-borne prolactin gains access to binding sites in the central nervous system and that a receptor-mediated, blood-to-cerebrospinal fluid transport process in the choroid plexus may be a major conduit for such uptake. Recent findings from several vertebrate species also suggest that the brain may synthesize one or more prolactin-like molecules that could conceivably interact with these binding sites. Direct actions of prolactin and related hormones on brain mechanisms underlying reproductive processes are suggested by the profound dose-dependent suppression of gonadotropin secretion and gonadal activity in ring doves by intracerebroventricular administration of prolactin or growth hormone at doses that are below those required for significant peripheral actions. A major challenge for future investigation will be to identify the brain site(s) at which these and other effects of prolactin are exerted and to determine how blood-borne prolactin of pituitary origin, prolactin-like molecules of brain origin, and growth hormone-like molecules interact with each other and with other neurochemical systems to promote these types of changes under normal physiological conditions.
SYNOPSIS. Data from the literature and from our own studies on the receptors for prolactin (PRL) and growth hormone (GH) are reviewed and analyzed. Receptors for PRL have been studied in a wider range of species and in a greater diversity of target organs than have the binding sites for GH. Although GHs are structurally more highly conserved among the vertebrates than are PRLs, the available data indicate that there is greater diversity among GH receptors than there is among PRL receptors. In general, GH receptors show greater species specificity but less hormone specificity than do PRL receptors. The reason for the greater diversity among GH receptors as compared to PRL receptors is unknown; it bears no relationship to phylogeny.
Data on the binding of purified preparations of mammalian PRL, GH and placental lactogen (PL) to renal and hepatic receptors for PRL and GH, respectively, of several vertebrate species are reviewed. The species and hormone specificity of the binding of the hormones to the two typesof receptors showed no consistent pattern. To explain this disarray, we propose that the receptor binding domains of PRL and GH were present in their common ancestral gene and that they havebeen retained to variable degrees by all of the descendant members of the PRL-GH family. We further propose that hormone and species specificity of binding is determined by hindering features on the hormones and on the receptors, rather than by merely the presence or absence of the appropriate binding determinants.
Twenty-one mated bitches were used, some of them repeatedly, to study the effect of an ergot alkaloid derivative, cabergoline (CAB), on ovarian endocrine function during early- to mid-luteal phase and late-luteal phase of gestation. In a blind trial, twelve bitches were bred three times; six of them received a daily dose of 5 mcg/kg body weight (BW) for 28 d, starting the day after the third breeding; the remaining six bitches received a placebo. In open trials, three bitches were given 15 mcg/kg CAB, and one bitch was given 5 mcg/kg daily for 5 d, around four wk of pregnancy (mid-luteal phase). Bight bitches were given 5 mcg/kg CAB once daily for 5 d, around 6 to 7 wk of pregnancy (late-luteal. phase). All dogs treated during the early- to mid-luteal phase maintained pregnancies. However, abortion resulted during or after CAB treatment during the late-luteal phase. Prolactin levels were determined in four bitches (late-luteal phase), and they showed a drop to baseline levels within 24 h after the first treatment with CAB. Progesterone blood levels always dropped in response to CAB treatment, but they reached baseline levels within 48 h only in bitches treated after mid pregnancy. These results indicate that CAB is not sufficiently luteolytic during the first half of pregnancy; however, it is fully luteolytic during the second half and can be used as an abortifacient during this period.
Plasma prolactin secretion during the luteal phase and pregnancy was studied in 11 mated but non-parturient and 26 parturient blue fox vixens. Prolactin was measured in blood plasma once or twice a week using a heterologous double-antibody radioimmunoassay. Data for all females were fitted with an animal model. In both groups of females, prolactin concentrations increased slowly during the early post mating period. For the parturient vixens the prolactin values increased further until parturition, whereas there was only a slight increase in the non-parturient vixens. Statistically significant differences (p < 0.05) were observed in prolactin release between the non-parturient and parturient animals from day 36 after mating. A possible role of prolactin may exist in the luteotrophic complex maintaining pregnancy in blue fox vixens, because higher levels of plasma prolactin and progesterone appeared in the parturient vixens compared to the non-parturient during the second half of gestation.
From 1980 to 1989, experiments were conducted on 28 intact (13 females, 15 males) and 10 neutered wolves (5 females, 5 males) to characterize prolactin (PRL) release. From these studies, we have (i) adapted and validated the canine PRL radioimmunoassay of Parlow for wolves; (ii) determined that the plasma half-life of PRL is 44 min; (iii) demonstrated that anesthesia with 400 mg ketamine plus 50 mg promazine, 400 mg ketamine plus 30 mg xylazine, or 7.5 μg∙kg−1 etorphine plus 0.5 mg∙kg−1 xylazine, administered intramuscularly, does not alter PRL rhythms or control mechanisms; (iv) indicated that PRL is not secreted in response to handling stress (P ≥ 0.78) or by activation of the hypothalamic–pituitary–adrenocortical axis simulated by intravenous injection of 50 μg ovine corticotropin-releasing factor (P = 0.28); (v) demonstrated a circannual rhythm in intact and neutered wolves characterized by elevated PRL levels just prior to summer solstice; (vi) detected a circadian PRL rhythm in females; (vii) provided evidence for dopaminergic control of PRL secretion by injecting 2.0 mg∙kg−1 promazine, a dopaminergic antagonist, which increased PRL levels significantly (P = 0.0001); (viii) shown that intravenous injection of 100 μg thyrotropin-releasing hormone results in PRL release (P = 0.0001), but that this release could not be attenuated by prior administration of 1.0 mg∙kg−1 of the opioid antagonist naloxone; (ix) determined that feeding 2.0 mg of melatonin daily reduced basal PRL levels in May and June (P = 0.03), but not in October–December (P = 0.42), and that PRL stimulation with 100 μg thyrotropin-releasing hormone was consistently lower in melatonin-fed wolves; and (x) shown that pinealectomy does not abolish the circadian PRL rhythm nor alter absolute PRL levels relative to sham-operated control wolves (P = 0.33).
A hypothalamic role in the aetiology of hypertension in the spontaneously hypertensive rat (SHR) has been suggested by prior observations. In an attempt to determine whether the central control of prolactin (PRL) release is altered in the SHR we have compared the PRL response to immobilization stress, thyrotrophin releasing hormone (TRH), haloperidol, and L-DOPA in the SHR and in normotensive Wistar control rats. Carotid artery catheters were inserted 48 h prior to the PRL response studies and the catheters were maintained patent with heparinized saline. Timed blood samples were obtained in SHR and control rats weighing 180-225 g. The SHR demonstrated elevated basal serum levels of PRL and greater PRL responses to stress. However, administration of L-DOPA resulted in a similar suppression of serum PRL in the SHR and in the normotensive controls. These findings suggest alteration in the central control of PRL release in the SHR. Observations of elevated basal PRL, exaggerated PRL in response to L-DOPA in SHR are consistent with normal pituitary responsiveness to dopamine suppression of PRL release, but defective hypothalamic metabolism of dopamine. Alterations in central dopamine control mechanisms in the SHR may play a role in the pathogenesis of essential hypertension in these animals.
On the basis of the results of investigations from systemic tolerance tests (and carcinogenicity studies), an attempt is made to evaluate the effects of various progestagens, oestrogens and progestagen-oestrogen combinations on the mammary gland of the dog. The interpretation of such effects in the dog and its relevance in predicting a tumorigenic effect of contraceptive steroids in man is discussed in the light of comparative endocrinology of reproduction. The induction of mammary gland tumours in dogs by certain progestagens or progestagen-oestrogen combinations must be considered as being a species-specific effect, related to the high hormonal potency (progestational activity) of these compounds in the dog and their stimulatory effect on canine growth hormone. Based on the present state of our knowledge and because of the marked interspecies differences of action of contraceptive steroids in dog and man, the steroid-related canine mammary tumours, especially with regard to the doses necessary for contraception, are unlikely to be indicative of a potential hazard to the human female.
Lactation is usually differentiated into three stages - mammary growth, initiation of milk secretion and maintenance of established milk secretion. Each stage is regulated by a complex of metabolic and reproductive hormones: prolactin, growth hormone, corticoids, thyroxin, insulin and, especially for mammary growth, oestrogens and progesterone. For lactation to be maintained the mammary gland must also be stimulated by suckling (or milking) and ejection of milk. The effects of hormones on established lactation differ from species to species. Prolactin seems to play a central part in the hormonal control of lactation. Suckling, milking or other stimulation of the teat seems to be an adequate physiological stimulus for the release of prolactin and of oxytocin (which is essential for milk ejection). Two compounds, both of which are potent in human and animals, are helpful in investigations of the physiological role of prolactin in lactation in vivo: a specific inhibitor of the release of prolactin, the synthetic ergot alkaloid bromocriptine (2-bromo-α-ergocriptine, CB154), and a stimulator, the synthetic tripeptide of hypothalamic origin - thyroliberin (TRH). Experiments with these compounds indicate that large concentrations of prolactin in the circulation (especially after milking) are not needed for lactation to be maintained in ruminants but that prolactin is essential for the onset of lactation in these species. In contrast, prolactin is an essential hormone for lactogenesis and galactopoiesis in monogastric species like the rabbit, rat, pig, dog and human. The suckling stimulus is necessary for the maintenance of lactation in these species.
Prolactin (PRL) and progesterone (P4) values were collected from eight intact (4 female, 4 male) mixed-breed dogs housed outdoors for a two-year span. A circannual component was significant for PRL for each dog (P less than 0.01) and the rhythm was validated for the population (P less than 0.004). Females had two estrus periods a year demonstrated by a P4 frequency of 23.5 +/- 0.47 wk. A 6-month component was statistically significant for P4 for three dogs and of borderline statistical significance for the fourth dog. Circannual acrophases yielded a statistically significant population rhythm (P = 0.012), whereas the 6-month component was of borderline statistical significance (P = 0.056). No time-macroscopic relationship between PRL cycles and P4 cycles was seen. These findings are consistent with similar PRL rhythms in non-domestic canids and emphasize the importance of considering seasonal effects when interpreting PRL data.
Cabergoline, a new ergoline derivative, is a potent prolactin inhibitor. In this review, results are combined from previously published and unpublished blind laboratory and open clinical studies with cabergoline in pseudopregnant, pregnant and lactating bitches, in bitches with normal and prolonged cycles, and in pregnant queens. Dose-response studies in nursing bitches, using puppy weight as an endpoint, revealed that a dose of 5 micrograms/kg/day orally (for 5 days) was the optimal dose with a minimum of side effects. This dose effectively lowered blood prolactin concentrations in pregnant bitches and was partly luteolytic during the 1st half of gestation, and fully luteolytic during the 2nd half of gestation. Consequently, pregnancies were terminated in the 2nd half of pregnancy in the bitch, and in the queen. Treatment successes with pseudopregnancy and true and false lactation, including cases of eclampsia, were greater than 90%. The same level of success was seen in bitches with prolonged cycles (anoestrus). A 7-10-day treatment period resulted almost uniformly in oestrus, and restored fertility in greater than 80% of all bitches mated. Cycles were occasionally shortened in bitches treated for false lactation. Attempts to shorten cycles routinely in beagle bitches, in a commercial breeding operation, with a dose of 5 micrograms/kg/day for 14 days during months 4, 5 or 6 of the cycle were unsuccessful.
Relatively little is known about hormonal mechanisms underlying paternal behavior in mammals. Male California mice, Peromyscus californicus, display extensive parental care toward their young. Parental behavior of fathers, expectant fathers (males living with their pregnant partner), and virgin males was assessed in a 10-min test with a 1- to 3-day-old alien pup. Few virgin males acted parental (19%) compared to fathers one day postpartum (80%) and expectant fathers (56%). Plasma prolactin levels were significantly elevated in fathers 2 days postpartum compared to expectant fathers and virgin males. Paternal prolactin levels were similar to those of mothers. There were no differences between groups in levels of plasma testosterone. These data suggest, contrary to other reports, that prolactin is a likely correlate of paternal behavior in rodents.
The short introduction gives a review on the complex of exogen and endogen opioids and their receptors as well as on their pharmacodynamics, pharmacokinetics and toxicity of naloxone. The clinical efficacy of naloxone as an opioid antagonist is described. Applications of naloxone for the dog are specified: antagonisation of etorphine, morphine, levomethadone and fentanyl, antagonisation of exogen and endogen opioids in puppies and treatment of lactomania in the bitch. The mean effective dose to antagonize morphines is 0.003 mg/kg bodyweight. If persisting analgesia is indicated the dose of naloxone in titrating steps in 0.001 mg/kg bw. To antagonize postpartal hypoxia in puppies 0.02 mg per animal naloxone have to be injected. For treatment of lactomania a dose of 0.01 mg/kg bodyweight twice a day for a couple of days is recommended. The clinical effectivity of naloxone is proved doubtlessly. Compatibility and safety are very high.
In contrast to the large variation in canine gestation lengths based on mating-to-whelping intervals (56 to 70 days), gestation length based on intervals from the preovulatory LH surge to whelping shows little variation (64 to 66 days). By considering the preovulatory LH surge as the central endocrine event of the fertile cycle, various events can be reasonably timed, including ovulation on day 2, oocyte maturation on day 4, reduced fertility after day 6, implantation around day 17, and development of fetal radiopacity after day 45. Throughout pregnancy, gestation is dependent on ovarian progesterone secretion and, thus, on pituitary LH and prolactin for luteotrophic support. Because prostaglandin F2 alpha is luteolytic in the bitch, it may be involved in the luteolysis observed immediately prepartum in association with rises in maternal cortisol and prolactin levels.
Present knowledge about the estrous cycle of the bitch has been reviewed from a morphological, endocrinological and clinical point of view. This cycle is truly biphasic, characterized by its slow motion. It includes pregnancy or pseudopregnancy, and lactation. Corpus luteum function and regression as well as endometrial recovery, following endometrial desquamation at about day 100 of the cycle, are finalized at about days 140 to 150. Soon thereafter, subclinical preparations for the next proestrus can be recognized. Prolactin seems to play an important role as a luteotrophic agent, beginning at about day 30 to 35 of the cycle. Inhibition of prolactin secretion can be used to induce abortion, or to inhibit lactation and to shorten the cycle, or to treat clinical anestrus. Late metestrus and subclinical proestrus, i.e. days 120 to 170 of the cycle, is the most suitable period of the cycle to initiate suppression of the cycle, i.e. prevention of the next estrus, by using progestins with the least tendency for side effects.
The seasonal changes in testicular weight in the blue fox were associated with considerable variations in plasma concentrations of LH, prolactin, androstenedione and testosterone and in FSH-binding capacity of the testis. An increase in LH secretion and a 5-fold increase in FSH-binding capacity were observed during December and January, as testis weight increased rapidly. LH levels fell during March when testicular weight was maximal. Plasma androgen concentrations reached their peak values in the second half of March (androstenedione: 0.9 +/- 0.1 ng/ml: testosterone: 3.6 +/- 0.6 ng/ml). A small temporary increase in LH was seen in May and June after the breeding season as testicular weight declined rapidly before levels returned to the basal state (0.5-7 ng/ml) that lasted until December. There were clear seasonal variations in the androgenic response of the testis to LH challenge. Plasma prolactin concentrations (2-3 ng/ml) were basal from August until the end of March when levels rose steadily to reach peak values (up to 13 ng/ml) in May and June just before maximum daylength and temperature. The circannual variations in plasma prolactin after castration were indistinguishable from those in intact animals, but LH concentrations were higher than normal for at least 1 year after castration.
Four beagle bitches were treated orally, twice daily with 250 micrograms bromocryptine, an inhibitor of prolactin secretion, from D1-D5 (D1 is defined as the first day of the luteal period) until the onset of the next prooestrus (n = 2) or the end of the luteal period (n = 2) of the following cycle. The mean interoestrous interval in the experimental group (123.3 +/- 23.1 day; n = 4) was significantly (p less than 0.001) shorter than the average of the mean values of the interoestrous interval (245.9 +/- 8.8 day; n = 36) of 10 control bitches. This shortening is mainly a consequence of a reduction to 35% of the anoestrous period of normally cyclic dogs. The luteal period of the first cycle was shortened to 78% compared with the luteal period of control dogs and this is also a contributing factor.
The annual cycle of the testicular function (testis and epididymis weights and plasma testosterone levels) were considered in relation to seasonal variations in plasma LH and prolactin concentrations in two wild European mammals: the badger and the fox. Phase relationships were established between the annual prolactin cycles and daylight duration. The influence of castration on the seasonal variations in plasma LH levels was also studied. The resumption of activity in the testicular function occurs during autumn for both species. The reproduction period begins in winter but it is over by the beginning of spring for the fox whereas for the badger it lasts until early summer. In the same way, the annual cycle of the gonadotrophic function which, in the fox, presents only one maximum at the end of autumn, is bimodal in the badger with one maximum in January and a second in June. On the other hand, both species have a similar annual prolactin cycle, which shows an increase from the winter solstice onwards, in synchronization with the increase in daily light duration. The highest prolactin levels are measured in spring followed by a decrease during summer. This result calls into question the role played by prolactin in the regulation of the testicular function in as far as the two species have an annual reproductive cycle of the 'short-day' type (onset of activity occurring before the winter solstice) but show seasonal prolactin variations similar to those described for 'long-day' species.
Speculations are made on the possible evolution and ontogeny of the functions of the hormone prolactin. The manifold actions of the hormone among the vertebrates are involved in five general kinds of physiological processes: osmoregulation, growth and development, metabolism, reproduction, and integumentary (ectodermal) actions. Osmoregulatory functions of the hormone predominate among fishes but are less prominent in tetrapods. Integumentary actions are proportionately more prevalent in fishes and amphibians than among reptiles, birds, or mammals. Growth and developmental, metabolic, and reproductive actions are proportionally more prevalent among the tetrapods than among fishes. Actions related to reproduction are particularly conspicuous in birds and mammals. Assuming that the prevalence of these different kinds of physiological actions of prolactin relate to the evolutionary history of its functions, the available data suggest that regulation of water and electrolyte homeostasis was the primal role of the hormone. Integumentary effects figure prominently in this primal function in fishes and amphibians. Growth and developmental actions and metabolic effects emerged subsequently, and reproductive functions became significant still later. Sparse information is available on the ontogeny of prolactin's functions, but some data indicate that the hormone is involved in osmoregulation and growth control in larval amphibians and possible in fetal and/or neonatal mammals. Prolactin's role in reproduction becomes prominent in adult tetrapods, especially in the homeotherms. Thus the available evidence suggests that the ontogeny of prolactin's functions does recapitulate the phylogeny of its physiological roles in vertebrate adaptation, at least in part.
The purposes of this study were (1) to evaluate the effects of cabergoline (1.65 micrograms kg-1 injected subcutaneously for 5 days) on plasma progesterone concentrations in the pregnant bitch; (2) to assess its clinical value in terminating pregnancy in the bitch, and (3) to evaluate its side effects. Cabergoline, given to pregnant bitches, had an anti-prolactinic action and induced abortion. Plasma progesterone concentrations were reduced to below that value necessary to maintain pregnancy (2 ng ml-1 in all cases when the treatment was given 40 days after the first mating, and in four out of six cases when given from 30 days after mating). Fetal resorption occurred in 75% of cases, without clinical sign other than some vaginal discharge. The efficiency of cabergoline treatment can be monitored by plasma progesterone determination: concentrations < 2 ng ml-1 5 days after the start of treatment indicate success; in the event of failure, another treatment can be started. Ultrasonography was not always useful in predicting abortion, as in some cases this was not preceded by signs of fetal distress. The use of cabergoline as an abortifacient in the bitch appears to be of interest. Its efficacy in the second half of gestation, which is attributable to its antiprolactinic action, has been widely demonstrated and the probable multifactorial regulation of corpus luteum activity during the first half of gestation has suggested that earlier luteolysis could certainly be obtained without any side effects through a multiple approach, using different, mutually potentiating, luteolytic agents.(ABSTRACT TRUNCATED AT 250 WORDS)
"Prolactin injection" is presented as a new contraceptive method. The method was tested in dogs. The dogs in the test group were injected with prolactin (PRL) in a dose of 600 micrograms/kg of body weight weekly for 6 months. During this period, the testicles, semen, reproductive hormones, renal function, and serum sodium and potassium were examined periodically. Testicular biopsy was obtained after 3 and 6 months of PRL injection. These investigations were repeated during the 6 months following withdrawal of the drug. Sperm count decreased to azoospermia in 3 months after PRL administration with decrease of sperm motility and increase of abnormal forms. Testicular biopsy showed degenerated seminiferous tubules. Reproductive hormones, renal function, and serum sodium and potassium revealed insignificant change (P > 0.05). Dog mating during the period of PRL administration induced no pregnancy. After 3 months of drug withdrawal, the sperm count normalized and dog mating produced pregnancy; offsprings showed no anomalies. The study demonstrates that PRL administration has the potential to be developed as a reversible male contraceptive.
Plasma luteinizing hormone (LH), prolactin and oestradiol concentrations and responses to a standard challenge with a gonadotrophin-releasing hormone (GnRH) analogue were measured at defined stages of consecutive oestrous cycles in beagle bitches. In each of 35 sampling sequences blood samples were collected every 20 min for 6 h followed immediately by injection of a GnRH analogue (GnRH-A) and collection of further samples after 10, 20, 40 and 60 min. Cycle stages were based on progesterone profiles and the day of the preovulatory LH peak. Sampling sequences were obtained during the luteal phase (n = 5), transition to anoestrus (n = 10), anoestrus (n = 17) and pro-oestrus (n = 3), which were 154-71, 114-44, 85-11 and 7-1 days before the preovulatory LH peak, respectively. Pulsatile LH secretion occurred spontaneously at all stages of the cycle and there was no effect of cycle stage on mean LH concentration or variability. In contrast, oestradiol was undetectable in most samples from early and mid-anoestrus until approximately 1 month before the preovulatory LH peak, after which average oestradiol concentrations and between-sample variability appeared to increase. Mean (+/- SEM) oestradiol concentrations for all preinjection samples collected from 100-75, 74-50, 49-25, 24-10 and 9-1 days before the LH peak was 1.4 +/- 0.1, 1.3 +/- 0.1, 2.4 +/- 0.3, 11.0 +/- 1.4 and 36.0 +/- 3.2 pg ml-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
A feral cat population (12 females, 13 males) was observed almost daily for 6 years, at a location 40.53 degrees N and 74.29 degrees W. Cats were accustomed to twice-daily feeding. Oestrous behaviour was seasonal and started in early January, irrespective of climatic conditions, with peak levels of oestrous activities in late January and February. Of all 60 heat periods observed, and conceptions recorded, the percentage occurrence was 58 and 49 in the first quarter, and 29 and 33, 12 and 16 and 1 and 2 in the second, third and fourth quarter, respectively. Queens could be reliably identified as being pregnant by 31.5 +/- 5.82 days, and were subjected between days 36 and 57 of gestation to daily oral treatment with 5-15 micrograms cabergoline kg-1 placed on food. Treatments (n = 41) from days 36 +/- 6.17 to 40.8 +/- 6.96 resulted in abortion in all animals on day 40.5 +/- 6.19; if treatment started as late as day 48.5, and lasted 9 or more days, premature parturition occurred. As cabergoline had caused mammary gland regression within 36-48 h, litters could not be nursed and perished quickly. Five repeatedly aborted queens were subsequently allowed to go to term. Pregnancies, gestation length (64.5 days), parturitions, maternal care and lactations were normal. Of the 24 kittens born out of seven pregnancies, 16 were observed from 6 months to 3 years. Pubertal oestrus and first conceptions occurred at 189.9 days (range 150-214 days) and 212.0 days (155-277 days), respectively. Males were seen to achieve reproductive success in their third year only.
This study in cats compared the effects of a natural prostaglandin F2 alpha (PGF2 alpha) and cabergoline, administered on and after day 30 after mating, with regard to the plasma progesterone concentration, the induction of abortion and the side effects of each regimen. PGF2 alpha, through a direct luteolytic action, induced abortion by an abrupt and rapid (24 h) decline in the plasma progesterone concentration. Using doses (2 mg per cat) comparable to the ones selected in a previous study, 100% of abortions (4/4) in cats treated from day 33 of gestation were obtained. Cabergoline (1.65 micrograms kg-1 day-1, administered subcutaneously for 5 days), through its antiprolactinic action induced abortion in 80% (4/5) of the cats treated on day 30 of gestation. The abortion was initiated by means of a reduction in plasma progesterone concentration to < 1 ng ml-1. This reduction was not as rapid (3-4 days), however, as that obtained with PGF2 alpha (24 h). Prostaglandins always induced significant side effects such as nausea, prostration, vomiting and diarrhoea, within 10 min following injection, whereas cabergoline never induced side effects or behavioural disturbances. In addition, cabergoline usually induced abortion through fetal resorption (75% of cases), without any clinical sign other than some vaginal discharge.
Twenty beagle bitches were treated with metergoline (groups I and II), ten with pregnant mares' serum gonadotrophin (PMSG; group III) and ten served as an untreated control group. Metergoline (12.5 mg per bitch) was injected intramuscularly (i.m.) every 3 days, starting between days 78 and 161 after the previous pro-oestrus. In 18 of the metergoline-treated bitches the interpro-oestrous interval (144 +/- 29 days) was significantly shorter (P < 0.01) than that of the control group (206.7 +/- 29.7 days). Of these 18 responder bitches, ten had not received human chorionic gonadotrophin (hCG) whereas eight had received 500 iu hCG i.m. in late pro-oestrus (group II). The durations of pro-oestrus and oestrus of the ten responding bitches not given hCG (6.8 +/- 5.5 and 11.7 +/- 4.5 days, respectively) did not differ (P > 0.05) from those of the control group (7.8 +/- 3.6 and 11.2 +/- 3.2 days). All ten bitches ovulated and nine became pregnant. Two of eight bitches responding to metergoline in group II exhibited a prolonged pro-oestrus after injection of hCG. In the remaining six bitches, the average duration of pro-oestrus and oestrus was 4.8 +/- 1.7 and 6.5 +/- 2.8 days, respectively, which was significantly shorter (P < 0.05) than in bitches not given hCG. The incidences of ovulation (6/8) and gestation (4/8) were lower than in bitches that received metergoline alone, or in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Studies in the female domestic dog demonstrate that luteinizing hormone (LH) and follicle-stimulating hormone (FSH) have secretion patterns that are pulsatile, are inhibited by oestradiol during pro-oestrus and surge to maximal values before ovulation. Studies in ovariectomized bitches suggest that the periovulatory surge is triggered by a preovulatory decline at late pro-oestrus in the oestrogen:progesterone ratio. During the 3-8-month non-seasonal anoestrus, FSH concentrations usually are 50-100% of those of the periovulatory peak, whereas LH concentrations are only 10-20% of peak values. In ovariectomized bitches FSH concentrations are often 5-10 times preovulatory peak values, whereas LH concentrations are only the same as, or double, peak values. Increased LH concentration and pulse frequency are associated with the termination of anoestrus. Treatment with gonadotrophin-releasing hormone (GnRH) pulses or infusions of GnRH agonists can induce fertile oestrus in early anoestrous bitches, as can treatment with a dopamine agonist, presumably by suppression of prolactin secretion. Between 4 months of age and pubertal pro-oestrus at 8-12 months of age, serum concentrations of FSH and LH are similar to those in adult anoestrus, and are suppressed during chronic infusion of GnRH agonist. The latter resulted in a reversible inhibition of puberty during 1 year of treatment. Studies in vivo have shown that LH and prolactin are luteotrophic throughout most of the luteal phase. LH stimulated progesterone synthesis by bitch luteal cells in vitro in the presence or absence of stimulant factors or steroid precursors present in serum.
Puberty in the female cat occurs between the ages of 8 and 10 months. Cats are seasonally polyoestrous, reflex ovulators. The oestrous cycle can occur as often as every 2-3 weeks. Ovulation usually occurs 24-36 h after copulation, and implantation occurs 12-13 days after copulation. The duration of gestation in the cat is 64-67 days (average 66 days). The corpora lutea secrete increasing amounts of progesterone, starting 1-2 days after ovulation. If implantation occurs, progesterone concentrations continue to increase throughout days 25-30, then slowly decline throughout the rest of pregnancy. In the absence of pregnancy, the corpora lutea reach their peak progestational activity within 10-15 days and then decline, with basal progesterone values being noted by days 30-35. Relaxin is produced by the fetoplacental unit beginning at about day 20 of gestation and continuing throughout the rest of pregnancy. Prolactin production increases from about day 35. Like those of prostaglandin F2 alpha, concentrations of prolactin plateau at about day 50 and increase abruptly just before delivery.