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Stress Hormones - Their Interaction and Regulation
Abstract
Stress stimulates several adaptive hormonal responses. Prominent among these responses are the secretion of catecholamines from the adrenal medulla, corticosteroids from the adrenal cortex, and adrenocorticotropin from the anterior pituitary. A number of complex interactions are involved in the regulation of these hormones. Glucocorticoids regulate catecholamine biosynthesis in the adrenal medulla and catecholamines stimulate adrenocorticotropin release from the anterior pituitary. In addition, other hormones, including corticotropin-releasing factor, vasoactive intestinal peptide, and arginine vasopressin stimulate while the corticosteroids and somatostatin inhibit adrenocorticotropin secretion. Together these agents appear to determine the complex physiologic responses to a variety of stressors.
... CRF, in turn, triggers the secretion of adrenocorticotropic hormone (ACTH) from the pituitary glands. ACTH, in turn, stimulates the release of cortisol and other Complex Trauma and Complex PTSD 21 glucocorticoids from the adrenal glands and catecholamines from the adrenal medulla and sympathetic nerves (Axelrod & Reisine, 1984.) Cortisol has a dual role in helping the body respond to stress. ...
... A controlled study by Heim, Newport, Bonsall, Miller, & Nemeroff, (2001) on survivors of childhood abuse used a standardized HPA axis challenge test, using synthetic administration of CRF to stimulate the HPA axis in subjects. As cited earlier, Complex Trauma and Complex PTSD 25 CRF is the first in the cascade of HPA neurohormones which lead to glucocorticoid release (Axelrod & Reisine, 1984). The study found heightened ACTH but blunted cortisol response to synthetic CRF administration in childhood abuse survivors without major depressive disorder, suggesting an enhanced glucocorticol negative feedback inhibition similar to that found in PTSD studies . ...
... A previous study of girls and women with early childhood sexual abuse also found blunted ACTH response to the administration of synthetic CRF (De Bellis et al., 1994) The blunted ACTH results in both studies point to the likelihood of a chronically over-active hypothalamus, leading to a down-regulation of the pituitary receptors for CRF resulting in blunted future ACTH responses . Down-regulation occurs when a flood of a particular neurohormone causes its receptors to decrease their binding capacity, essentially adjusting to the excessive availability of the hormone (Axelrod & Reisine, 1984). The chronic hypersecretion of CRF may also lead to down-regulation of CRF receptors at other sites beyond the HPA axis, potentially increasing vulnerability to anxiety and depression . ...
This paper aims to examine the profound impacts of complex trauma, the viability of complex PTSD as a diagnostic classification, and evidence for underlying psychobiological abnormalities in adults with complex trauma histories. A survey of the research literature on the psychobiology of trauma and traumatic stress, reveals that much of the preclinical work has been done on animals, and that the initial focus has been on veterans of the Vietnam war, and more recently, adult survivors of childhood sexual and physical abuse (Heim & Nemeroff, 2001). Complex PTSD was formulated to describe the impacts of chronic interpersonal trauma that includes victimization (Zlotnick et al., 1996). While complex PTSD was not designed to capture the effects of combat trauma, and captures a variety of traumatic experiences beyond childhood sexual and physical abuse, the limitations of the research literature have led this paper to rely heavily on studies of adult survivors of childhood sexual abuse and to include research on Vietnam war veterans for explanatory purposes.
Consistent with the research in the field, a number of the scientific findings presented here have been supported with the more comprehensive and detailed data available in studies of stress in animal. Due to the inconsistencies, contradictions and uncertainties inherent in the early literature of a new field, neurobiological research on traumatized children was examined but mostly not included in this paper. The research seems to indicate that, the neurobiological effects of trauma are different in traumatized children than in adults traumatized as children (Heim & Nemeroff, 2001). This may be due to the ongoing nature of neurodevelopmental processes in children or the presence of
continued or recent traumatization. Whatever the reason, child psychobiology differs substantially from adults, and is beyond the scope of this paper.
... For example, social stress activates the hypothalamic-pituitary-sympathetic adrenal (HPA) medulla system in animals [8]. HPA promotes the secretion of stress hormones, such as adrenocorticotropic hormone (ACTH) and corticosterone (CORT) [9][10][11][12]. These hormones work synergistically to relieve anxiety and aggressive emotions in animals under stress [10,13,14]. ...
... HPA promotes the secretion of stress hormones, such as adrenocorticotropic hormone (ACTH) and corticosterone (CORT) [9][10][11][12]. These hormones work synergistically to relieve anxiety and aggressive emotions in animals under stress [10,13,14]. High CORT levels under stress scenarios stimulate appetite and lead to increased food intake, which in turn leads to weight gain [10,15,16]. ...
... These hormones work synergistically to relieve anxiety and aggressive emotions in animals under stress [10,13,14]. High CORT levels under stress scenarios stimulate appetite and lead to increased food intake, which in turn leads to weight gain [10,15,16]. However, changes in food intake and body mass caused by stress have not been consistently researched. ...
Social animals enjoy colony benefits but are also exposed to social stress, which affects their physiology in many ways, including alterations to their energy intake, metabolism, and even gene expression. Aggressive calls are defined as calls emitted during aggressive conflicts between individuals of the same species over resources, such as territory, food, or mates. Aggressive calls produced by animals in different aggressive states indicate different levels of competitive intentions. However, whether aggressive calls produced in different aggressive states exert different physiological effects on animals has yet to be determined. Importantly, bats live in clusters and frequently produce aggressive calls of different syllables, thus providing an ideal model for investigating this question. Here, we conducted playback experiments to investigate the effects of two types of aggressive calls representing different competitive intentions on food intake, body mass, corticosterone (CORT) concentration, and gene expression in Vespertilio sinensis. We found that the playback of both aggressive calls resulted in a significant decrease in food intake and body mass, and bats in the tonal-syllable aggressive-calls (tonal calls) playback group exhibited a more significant decrease when compared to the noisy-syllable aggressive-calls (noisy calls) playback group. Surprisingly, the weight and food intake in the white-noise group decreased the most when compared to before playback. Transcriptome results showed that, when compared to the control and white-noise groups, differentially expressed genes (DEGs) involved in energy and metabolism were detected in the noisy-calls playback group, and DEGs involved in immunity and disease were detected in the tonal-calls playback group. These results suggested that the playback of the two types of aggressive calls differentially affected body mass, food intake, and gene expression in bats. Notably, bat responses to external-noise playback (synthetic white noise) were more pronounced than the playback of the two aggressive calls, suggesting that bats have somewhat adapted to internal aggressive calls. Comparative transcriptome analysis suggested that the playback of the two syllabic aggressive calls disrupted the immune system and increased the risk of disease in bats. This study provides new insight into how animals differ in response to different social stressors and anthropogenic noise.
... Figura 2: Comparativo dos níveis leucócitos entre os T1controle e T2 (uso de filtro ionizante -Íons Balls), no período de junho a dezembro de 2022, em uma propriedade leiteira localizada em Paulo Bento/RS. As respostas neuroendócrinas que se destacam em situações de estresse são: ativação do sistema nervoso autônomo (SNA), liberação de neurotransmissores noradrenérgicos e colinérgicos, acionamento do eixo hipotálamo -hipófise -adrenal (HPA), elevação nos níveis plasmáticos do hormônio liberador da corticotrofina (CRH), adrenocortrófico (ACTH), noradrenalina, adrenalina e cortisol (AXELROD; REISINE, 1984;MÖSTL;PALME, 2002). A avaliação dos níveis destes hormônios vem sendo utilizada para estudo de fatores estressantes para os animais (AXELROD; REISINE, 1984;MÖSTL;PALME, 2002), o nível plasmático de cortisol é classificado como o principal indicador de estresse, onde o aumento dos níveis de cortisol sérico sugere situações que são contrárias ao conforto e bem-estar animal (MOBERG, 1987;BROOM, 1991;MÖSTL;PALME, 2002), o cortisol proporciona uma diminuição na produção de IGF-1, juntamente com suas proteínas de ligação, ocasionando uma redução dos níveis de IGF-1 plasmática e sua eficiência (VEGA et al., 1991). ...
... As respostas neuroendócrinas que se destacam em situações de estresse são: ativação do sistema nervoso autônomo (SNA), liberação de neurotransmissores noradrenérgicos e colinérgicos, acionamento do eixo hipotálamo -hipófise -adrenal (HPA), elevação nos níveis plasmáticos do hormônio liberador da corticotrofina (CRH), adrenocortrófico (ACTH), noradrenalina, adrenalina e cortisol (AXELROD; REISINE, 1984;MÖSTL;PALME, 2002). A avaliação dos níveis destes hormônios vem sendo utilizada para estudo de fatores estressantes para os animais (AXELROD; REISINE, 1984;MÖSTL;PALME, 2002), o nível plasmático de cortisol é classificado como o principal indicador de estresse, onde o aumento dos níveis de cortisol sérico sugere situações que são contrárias ao conforto e bem-estar animal (MOBERG, 1987;BROOM, 1991;MÖSTL;PALME, 2002), o cortisol proporciona uma diminuição na produção de IGF-1, juntamente com suas proteínas de ligação, ocasionando uma redução dos níveis de IGF-1 plasmática e sua eficiência (VEGA et al., 1991). ...
O fornecimento e a utilização de água ionizada para a ingestão em animais de produção têm se tornado uma alternativa interessante para expressar benefícios, bem-estar, auxílio nos processos digestivos, além de auxiliar no equilíbrio do sistema imune. O presente trabalho avaliou o efeito do fornecimento de água ionizada para bovinos leiteiros, sob o sistema de criação compost barn, no município de Paulo Bento/RS. No trabalho, os animais foram divididos em dois tratamentos, sendo o Tratamento 1 composto por um grupo de 24 fêmeas primíparas, com peso corporal de 450 Kg, que não tiveram acesso à água sem o filtro ionizante (Íons Balls). O Tratamento 2 foi composto por 26 vacas, que tiveram no mínimo 3 e no máximo 6 partos, que possuíam peso corporal aproximado de 520 Kg, com acesso a água tratada com filtro ionizante (Íon Balls). Os animais do Tratamento 2 estavam com maior tempo de lactação quando comparados aos animais do Tratamento 1. Após os bovinos serem separados em dois grupos, selecionaram-se 08 animais de cada grupo para serem acompanhados e avaliados. As avaliações foram mensais, e analisou-se a produção de leite e Califórnia Mastite Teste (CMT). Para a análise sérica avaliaram-se os níveis de cortisol e hemograma. Quando o parâmetro avaliado foi a produção de leite não houve diferença estatística entre os tratamentos, embora acredita-se que o fornecimento de água ionizada para os animais do Tratamento 2 tenha contribuído para que ocorresse uma estabilização na diferença de produção entre os dois tratamentos. Na avaliação do Califórnia Mastite Teste (CMT) os animais do Tratamento 1 apresentaram uma incidência de mastite de 4,10 % dos quartos mamários analisados e o Tratamento 2 apresentou 6,77% dos quartos analisados, não apresentado diferença estatística. Quando foi analisado o hemograma, somente os níveis de leucócitos apresentaram diferença estatística, sendo a mesma encontrada na terceira coleta do experimento, onde o Tratamento 2 apresentou menor nível de leucócitos que o Tratamento 1. Na análise dos níveis de cortisol encontrou-se diferença estatística na segunda e quinta coleta, onde, em ambos os casos, o Tratamento 2 apresentou menores níveis de cortisol que o Tratamento 1. O método estatístico utilizado foi ANOVA, sob uma significância de 95%. Os resultados demonstram que o fornecimento de água ionizada para bovinos de leite, apresenta benefícios para os animais, tanto para seu bem-estar como no auxílio de estabilidade do sistema imune.
... Acute stress is a normal physiological and mental response to novel, unpredictable, threatening, and uncontrollable aspects of human experience (Gagnon & Wagner, 2016;McEwen, 2007). In humans, the stress response is generally thought to proceed in two phases, the first involving a relatively fast sympathetic adrenal medullary (SAM) response and the second a relatively slow hypothalamic-pituitary-adrenal (HPA) response (Angelova et al., 2021;Axelrod & Reisine, 1984;Buchheim et al., 2019;Charmandari et al., 2005;Gagnon & Wagner, 2016;McEwen, 2007;Padgett & Glaser, 2003). The release of stress-related neurotransmitters such as epinephrine, norepinephrine, and cortisol causes diverse effects on physiology, the brain, and behavior. ...
... First, we examined whether CES (versus placebo) might reduce pupil diameter and/or cardiorespiratory effects of an acute stress induction, such as by reducing heart rate or respiration rate and/or increasing heart rate variability. Second, we examined whether CES (versus placebo) might reduce the hormonal effects of an acute stress induction, such as by reducing salivary alpha amylase (as a proxy for SAM activity (Chatterton et al., 1996;Takai et al., 2004;Wetherell et al., 2006)) and/or cortisol (as a proxy for HPA activity (Axelrod & Reisine, 1984;Charmandari et al., 2005;McEwen, 2007)) responses to stress exposure. Third, we examined whether CES might modulate performance on cognitive tasks involving executive function, spatial orienting, and memory retrieval. ...
Cranial electrotherapy stimulation (CES) has a long history in the clinical sciences as a complementary therapy for treating disorders such as insomnia, depression, and anxiety. Research suggests that CES may also prove valuable for altering physiology and behavior in healthy, non-clinical samples, though data are equivocal and show a high risk of bias. The present study used a double-blind, placebo-controlled, crossover design to examine the effects of CES on emotional, physiological, biochemical, and behavioral responses to acute stress. Healthy male participants visited the laboratory for two sessions, one involving active CES administration (20 min at 100 µA and 0.5 Hz) and one involving sham, inactive CES. During each session, participants were placed under stress (threat of torso shock) while performing challenging cognitive tests, and we measured emotional, biochemical (alpha amylase, cortisol), physiological (heart rate, respiration rate, heart rate variability, pupil diameter), and cognitive behavioral (memory, decision-making, spatial orienting) responses. Outcome metrics were compared using repeated measures analysis of variance (ANOVA) and planned comparisons. The stress induction reliably modulated measures of sympathetic adrenal medullary (SAM) activity but not hypothalamic–pituitary–adrenal (HPA) axis activity. Active versus placebo CES did not significantly influence any emotional, biochemical, or physiological outcome measure. Active CES did, however, selectively increase performance on a recognition memory test and degrade performance on a perceptual decision-making test. Overall, we find no compelling evidence that CES reliably modulates the nervous system’s immediate response to acute stress, suggesting its limited utility for sustaining performance in high-stakes domains involving stress exposure.
... PNMT principally catalyzes the conversion of norepinephrine to epinephrine ( Figure 2A) and is mainly involved in the stress response. 20,21 Epinephrine is strongly correlated with mood alteration and depression. 22−25 In addition, several studies indicate a role for this hormone in the control of erection. ...
... 47 To response a stressful situation (emotional, environmental, or physical), the adrenal medulla rapidly releases the stored epinephrine into the general circulation. 21 This, in turn, leads to the subsequent release of cortisol in humans. The cooperation among these hormones produces different physiological responses involving central and sympathetic nervous system functions. ...
... In the short term, the response to a stressor is triggered by the activation of the sympathetic nervous system, which releases catecholamines (norepinephrine and epinephrine) from the adrenal medulla [15]. During this phase, motor activity and contractions of the heart and spleen increase, releasing more red blood cells; vasomotor adjustments and pupil dilation occur, blood coagulation increases, and lymphocytes are neutralised to repair tissue damage, while energy is increased through glycolysis and lipolysis [16]. In the longer term, the corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosteroids act thanks to the activation of the HPA [13]. ...
Rabbits are subjected to challenges that induce stress and require them to continuously adapt. Veterinary procedures represent an important source of stress. In other pets, pheromone use was shown to help patients better cope with these procedures. This study aimed to evaluate whether continuous exposure to the rabbit appeasing pheromone (RAP) could help rabbits cope with the stress induced by routine clinical consultations and vaccinations. Twenty-four 5-week-old rabbits were housed in two identical rooms for 43 days, one in which the rabbits underwent continuous RAP treatment and one with the placebo. The rabbits were vaccinated 8 days afterwards, and their behaviour was evaluated using visual analogic scales (VASs) and videos. The rabbits were also examined seven times, on a weekly basis, using VASs to assess their behaviour. The video analysis showed that the RAP-treated rabbits were less inhibited (p = 0.03) and more in contact with the surgeon (p = 0.039) during vaccinations, while the non-treated rabbits kept their ears in the middle/flattened position (p = 0.003). The RAP-treated rabbits were also less agitated (VAS analysis, p = 0.02). During the consultations, a treatment × day effect was observed in favour of the RAP group for the rabbit state and rabbit reactivity VAS analysis (p < 0.0001). These findings seem to suggest that continuous RAP exposure could be a promising tool for helping rabbits cope with veterinary procedures.
... Stimulation of the sympathetic-adrenomedullar axis leads to the secretion of E and NE (Ghosh et al. 2001;Konarska et al. 1989). A subsequent activation of the hypothalamic-pituitary-adrenocortical axis (HPA) results in corticosteroid secretion under pituitary ACTH stimulation released in response to the action of the hypothalamic corticotropin-releasing hormone (CRH) and arginine vasotocin (AVT) (Axelrod & Reisine 1984;Herman et al. 2016). AVT has a role in maintaining the water balance; thus, it may activate the HPA axis in cases of osmotic stress (Sharma et al. 2009). ...
Hrabia A.,Wolak D., Frydrych K., Gumułka M., Saito N., Sechman A. 2024. Is selected aquaporin expression in the chicken adrenal gland affected by disturbed sex steroid action? Folia Biologica (Kraków) 72: 118-129. In our earlier study, we demonstrated changes in the aquaporin 4 (AQP4) abundance in the reproductive system of hens following a fasting or tamoxifen (TMX; estrogen receptor modulator) treatment. In the present study, we examine the hypothesis that the expression of selected aquaporins (AQPs) changes in the avian adrenal gland under reduced circulating sex steroid hormone concentrations or a blockage of estrogen receptors. Accordingly, our aim was to examine the AQP1, AQP2, AQP4, AQP5 and AQP9 mRNA and/or protein expression and immunolocalisation in the adrenal glands of chickens after several days of fasting or TMX treatment. The hens were fasted or treated with TMX every day, until a pause in egg laying occurred in all the hens. Control hens were fed ad libitum or were treated with a vehicle, respectively. The hens were euthanised on Day 6 or 8 of the experiment, respectively, and the adrenal glands were collected. Subsequently, the gene and protein expressions of AQPs in the tissues were examined by quantitative real-time PCR and Western blotting, respectively. The fasting, which is accompanied by diminished plasma concentrations of sex steroids, caused a decrease in the relative abundance of AQP1, AQP2, and AQP9 mRNA transcripts, while the TMX treatment lowered the AQP2 and AQP4 mRNA transcript levels. However, the abundances of AQP proteins were not changed by the fasting and TMX treatment. Immunoreactivity for AQP1, AQP2, and AQP9 protein was localised to the adrenal gland chromaffin cells and adrenocortical cells; whereas for AQP4 it was localised exclusively to chromaffin cells. In summary, the selected AQPs seem to be important for the regulation of the water/glycerol transport required for the functioning of the hen's adrenal gland cells. An involvement of ovarian steroids, especially estradiol, in the regulation of the AQP expression is also suggested.
... (Axelrod, Reisine, 1984), 우울증과의 관련성 (Lloyd, 1980 (Brown et al., 1981) K r a n t z , 1 9 8 3 ： F o l k m a n 둥 1 9 8 0 ) , 보 편 적 으 로 장 업사회의 스트레스와 관련이 깊다고 할 수 있는 A형 행 동 특 성 에 대 한 연 구 가 많 이 행 해 지 고 있 디 -( 김 명 선 .1 9 9 7 ； F r i e d m a n , R o s e n m a n . 1 9 7 4 ； K a b a s a , M a d d i , K a h n , 1 9 8 2 ) . 이 행 동 특 성 은 항 상 시 간 에 쫓 동 을 취 하 는 것 이 아 니 며 . ...
This study was conducted to investigate the (x)ntent of stress coping behavior and to examine the relationship between behavior characteristics and stress coping behavior ir. university students.Survey was carried out on 386 university students with questionnaire which consisted of sociodemographic data, a scale for stress coping behavior, a scale for behavior characteristics.Data analysis procedure included factor analysis and multivariate regressions using stress coping behavior as a dependent variable, sociodemographic variables and behavior characteristics as independent variables.Analysis showedi 1. On the whole, the subjects showed a tendency to lack in positive stress coping behavior.2. There were significant gender differences in stress coping behavior Female students showed more tendency to take stress coping behavior positively than male students.3. Multiple regression analysis revealed that, the factors such as gender, behavior characteristics, native place, giade and tendency of vulnerability to stress were t,o be independently and significantly associated with stress coping behavior； for example, male, lower grade and urban-born students tended to take stress coping behavior negatively. The students who showed more subjective behavior characteristics and who had vulnerability to stress showed the same tendencies.In conclusion, this study suggests that it is important for late-adolescents to establish their subjective behavior characteristics, which would be helpful for them to cope with their stress well and would enable thein to keep their good mental health.
... It is produced by the adrenal glands and released into the bloodstream in response to various stimuli. EPI can act on different receptors throughout the body to produce a variety of physiological responses, such as increasing heart rate, blood pressure, and blood flow to the muscles, lungs, and brain, expanding airways, and releasing accumulated energy in the form of glucose [21]. EPI is widely used in medicine because it can counteract severe allergic reactions (anaphylaxis) and treat life-threatening conditions such as cardiac arrest and severe asthma attacks [20]. ...
Molecularly imprinted polymers (MIPs) are a growing highlight in polymer chemistry. They are chemically and thermally stable, may be used in a variety of environments, and fulfill a wide range of applications. Computer-aided studies of MIPs often involve the use of computational techniques to design, analyze, and optimize the production of MIPs. Limited information is available on the computational study of interactions between the epinephrine (EPI) MIP and its target molecule. A rational design for EPI-MIP preparation was performed in this study. First, density functional theory (DFT) and molecular dynamic (MD) simulation were used for the screening of functional monomers suitable for the design of MIPs of EPI in the presence of a crosslinker and a solvent environment. Among the tested functional monomers, acrylic acid (AA) was the most appropriate monomer for EPI-MIP formulation. The trends observed for five out of six DFT functionals assessed confirmed AA as the suitable monomer. The theoretical optimal molar ratio was 1:4 EPI:AA in the presence of ethylene glycol dimethacrylate (EGDMA) and acetonitrile. The effect of temperature was analyzed at this ratio of EPI:AA on mean square displacement, X-ray diffraction, density distribution, specific volume, radius of gyration, and equilibrium energies. The stability observed for all these parameters is much better, ranging from 338 to 353 K. This temperature may determine the processing and operating temperature range of EPI-MIP development using AA as a functional monomer. For cost-effectiveness and to reduce time used to prepare MIPs in the laboratory, these results could serve as a useful template for designing and developing EPI-MIPs.
... In this axis, corticotropin-releasing hormone or factor (CRF), cortisol, and adrenocorticotropin hormone (ACTH) play a crucial role. Several neurotransmitters such as oxytocin, epinephrine, norepinephrine, 3-endorphin, vasopressin, serotonin, and angiotensin II are known to respond the stress stimuli [15][16][17]. These are also called stress hormones because of their primary role in stress response. ...
Infertility is a crucial and common health issue worldwide, that affects people both physiologically and psychosocially. The condition is described as the disease of the reproductive system of either male or female or both, incapability to instate a pregnancy after one year or more than twelve months of regular unprotected sexual intercourse or six months for women aged 35 years or more. Presently, the etiology of infertility is not well understood, many genetic factors, lifestyle factors, and environmental conditions such as stress work, oxidative stress, unbalanced nutrition, and unhealthy dietary patterns have been implicated to interfere with reproductive safety in both the sex. The nutritional factors are known to be amenable to normal and healthy reproductive function in both males and females. According to many studies, increased energy intake, dietary behavioral change, and low physical activity are responsible for epidemic disorders such as diabetes, heart disease, and obesity that affect reproductive health as well, and clear evidence indicates that there is a connection between inappropriate nutrition and sperm quality. Endocrinal disruption, occupational stress, and lifestyle behavior are positively linked with the pathophysiology of infecundity. Imbalance intake of both macro and micronutrients negatively affects normal reproductive function. Changes in eating behavior, and unhealthy dietary patterns such as a higher intake of food prepared with saturated and trans fats, spicy and salty foods, and a lower intake of antioxidants including fruit and vegetables are associated with reproductive life. This narrative review summarized that many studies with more consumption of fruit, vegetables, whole cereals, meat, poultry, skim milk, and seafood and less consumption of fried, spicy, salty, sugary, processed cereals and meats are linked with good sperm count.
... mg/kg, p.o.) (A), a GABA A receptor modulator ganaxolone(10,20,30 mg/kg, i.p.) (B), or a GR antagonist CORT113176(40,80, 160 mg/kg, p.o.) (C) once daily from postpartum day 0 to 24 h prior to sampling at postpartum day 9. Post-delivery treatment with only the GR antagonist at 40 and 80 mgNo effect of a GR antagonist, a SSRI, and an allopregnanolone analog on body weight. A, CORT113176 (80 mg/kg, p.o., once daily from gestation day 14 to 24 h prior to behavioral testing), a selective GR antagonist, did not affect body weight after the forced swim test at postpartum day 8 in either group. ...
... The released stress hormones inhibit insulin production, affecting the synthesis of metabolites such as glucose, lactate and uric acid (UA), as well as narrow arteries, boosting cardiac activities. By monitoring these stress-relevant biomarkers, it is possible to develop a comprehensive and objective health profile relating biophysical and biochemical signals to dynamic stress response monitoring [21][22][23] . ...
Approaches to quantify stress responses typically rely on subjective surveys and questionnaires. Wearable sensors can potentially be used to continuously monitor stress-relevant biomarkers. However, the biological stress response is spread across the nervous, endocrine and immune systems, and the capabilities of current sensors are not sufficient for condition-specific stress response evaluation. Here we report an electronic skin for stress response assessment that non-invasively monitors three vital signs (pulse waveform, galvanic skin response and skin temperature) and six molecular biomarkers in human sweat (glucose, lactate, uric acid, sodium ions, potassium ions and ammonium). We develop a general approach to prepare electrochemical sensors that relies on analogous composite materials for stabilizing and conserving sensor interfaces. The resulting sensors offer long-term sweat biomarker analysis of more than 100 h with high stability. We show that the electronic skin can provide continuous multimodal physicochemical monitoring over a 24-hour period and during different daily activities. With the help of a machine learning pipeline, we also show that the platform can differentiate three stressors with an accuracy of 98.0% and quantify psychological stress responses with a confidence level of 98.7%.
... The activation of stress responses involves an acute increment of glucocorticoid blood levels in order to quickly recover homeostasis, a state of steady internal conditions for optimal body function (Axelrod and Reisine 1984;Charbonnel et al. 2008a;Coutinho and Chapman 2011;Vitousek et al. 2018). However, long-term exposure to stressors results in a chronic glucocorticoid overproduction that may have detrimental physiological consequences, compromising the maintenance of homeostasis, and eventually affecting survival (Carrasco and Van de Kar 2003). ...
Rodent populations often undergo large, regular fluctuations. We studied immunological condition and physiological stress in the common vole and how it varied with environmental factors linked with population fluctuations, namely flea and Francisella tularensis (the bacterium causing tularemia) prevalence. We used two leukocyte indices, neutrophil-to-lymphocyte ratio (N:L) and proportion of eosinophils, as physiological long-term stress indicators, and measured levels of immunoglobulins (Ig) as a generic index of immunological condition. Leukocyte indices showed a hump-shaped relationship with Ig levels, consistent with an interdependence between physiological stress and immunological condition. N:L was negatively associated with vole density only in males. Eosinophil proportion was explained by the interaction between flea burden and tularemia prevalence, with highest levels in flea-infested voles also infected with tularemia. Ig levels did not vary with sex or flea prevalence but increased in tularemia-infected voles. When Ig levels were included as covariates in our models, the associations between leukocyte indices and environmental factors remained significant. Results suggest sex-specific associations between physiological stress and population density, and an influence of tularemia infection depending on ectoparasite load. We recommend using immunological parameters complementarily to leukocyte indices when studying physiological stress and infection dynamics in wild populations.
... To gain control over these modalities, it may be appropriate to maintain the balance between these two routes, ROS and RNS [37]. Free radicals are thought to be extremely harmful in the emergence of many pathological illnesses, such as cancer, inflammation, and neurological disorders [38][39][40]. The endogenous antioxidant system feeds them electrons to stabilize them and halt further oxidation. ...
Background: Several pathogenic conditions leading to morbidity, including cancer, aging, diabetes, reperfusion injury, cardiovascular disease, and neurological disorders, are known to be exacerbated by oxidative stress. Antioxidant therapy is effective in the treatment of such disorders and appears to be a potential therapeutic technique to reduce oxidative stress. The aim of our study is to investigate the antioxidant effects of L-ascorbic acid and nitric oxide (NO) modulators on rats suffering from oxidative stress induced by acute restraint stress (RSx1).
Methodology: In this in vivo study, Wistar rats were subjected to one hour of restraint stress on day 21 to induce oxidative stress. Superoxide dismutase (SOD), total antioxidant capacity (TAC), catalase, glutathione (GSH), and malondialdehyde (MDA) were used to assess the antioxidant effects. IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp. was used for data analysis.
Results: Compared to vehicle groups, acute restraint stress (RSx1) dramatically increased MDA levels while decreasing GSH, SOD, total antioxidant capacity, and catalase. L-NAME, 7-NI, AG (50 mg/kg each), and L-ascorbic acid (200 mg/kg) reversed the changes in SOD, MDA, GSH, total antioxidant capacity, and catalase levels. The NO precursor L-arginine (1000 mg/kg) and NO synthase inhibitors followed the same trend.
Conclusion: Our study findings highlight the complex role of antioxidants and NO modulators in the pathogenesis of diseases, as evidenced by the reversal of oxidative stress indicators. Antioxidant therapy, with its potential to mitigate oxidative stress, emerges as a viable treatment option for a range of pathological conditions associated with oxidative stress.
... Consequently, animals have physiological and behavioural mechanisms that allow them to respond to these challenges (Deak, 2007;Möstl & Palme, 2002). One of these mechanisms is the stress response, which begins with hypothalamic-pituitary-adrenal (HPA) axis activation and hormone (cortisol or corticosterone) release from the adrenal cortex (Axelrod & Reisine, 1984;Deak, 2007). At basal concentrations under normal conditions, glucocorticoids regulate metabolism and energy mobilization for everyday activities (Busch & Hayward, 2009), while at stressinduced concentrations, they provide an immediate energy supply and induce a cascade of adaptive physiological and behavioural responses (Deak, 2007;Sapolsky et al., 2000). ...
Captivity can alter the stress physiology and behaviour of an animal in both the short‐ and long‐term through repetitive exposure to novel stressors and, subsequently, may reduce the success of conservation efforts such as translocation and reintroduction. The Tasmanian devil (Sarcophilus harrisii) is threatened with extinction from a fatal facial tumour disease which has led to the establishment of an insurance meta‐population designed for future reintroductions of disease‐free devils. The meta‐population is comprised of intensive captive and free‐range captive environments; however, no study has yet examined the long‐term physiological implications of captivity on devils. We used non‐invasive faecal glucocorticoid metabolite (FGM) monitoring to determine if there were any differences in adrenal activity among intensive captive, free‐range captive and wild devils. FGM levels were not age or sex dependent, and we found that all population types had similar intra‐population variability and mean FGMs. In conclusion, both types of captive environment appear to maintain stress profiles similar to wild devils. image
... Stress is elicited by the inherent novelty, uncontrollability, unpredictability, or threatening nature of human experience (McEwen, 2007;Gagnon and Wagner, 2016), and is considered a normal physiological and mental response to such challenges. Stress carries diverse neurotransmitter, hormonal, genomic, and immune implications through its activation of the autonomic nervous system and hypothalamic-pituitary-adrenal (HPA) axis (Axelrod & Reisine, 1984;Padgett and Glaser, 2003;Charmandari et al., 2005;McEwen, 2007;Gagnon & Wagner, 2016;Buchheim et al., 2019;Angelova et al., 2021). Two systems are generally implicated in the body's response to stress exposure. ...
Military operations are characterized by high levels of stress and uncertainty, and these states can influence cognitive and physical performance outcomes. These states, however, can be difficult to reliably induce in laboratory contexts, making it challenging to quantify and model their influences on perceptual and cognitive processes underlying performance on applied tasks. Herein we describe the development and validation of a novel scenario-based virtual reality methodology, the decision making under uncertainty and stress (DeMUS) scenario, that accomplishes four primary goals. First, it induces physiological and biochemical stress responses through a threat of shock manipulation. Second, it induces transient states of uncertainty by manipulating stimulus clarity in a perceptual decision-making task. Third, it generates several performance metrics regarding recognition memory, spatial orienting, threat classification, and marksmanship decision making. Finally, the task combines behavioral, physiological, and biochemical measures to provide a more comprehensive understanding of how stress and uncertainty influence applied task performance. To provide an initial validation of the scenario and its associated tasks and measures, we conducted a pilot study ( n = 18) involving stress induction and cognitive performance assessment. Analyses revealed that: 1) the DeMUS scenario elicited tonic and phasic biochemical (salivary alpha amylase and cortisol) and physiological (heart rate, pupil diameter) stress responses, 2) the scenario elicited variable sympathetic autonomic nervous system and hypothalamic-pituitary adrenal (HPA) axis responses, and 3) stress influenced some measures of memory and decision-making in both negative and positive directions. Continuing research will assess individual- and group-level predictors of performance on these virtual reality tasks, and emerging performance enhancement techniques that can help military personnel sustain performance during stressful operations.
... Consequently, animals have physiological and psychological mechanisms that allow them to respond to these challenges (Deak 2007;Möstl and Palme 2002). One of these mechanisms is the stress response, which begins with hypothalamicpituitary-adrenal (HPA) axis activation and glucocorticoid hormone (cortisol or corticosterone) release from the adrenal cortex (Axelrod and Reisine 1984;Deak 2007). At basal concentrations in normal conditions, glucocorticoids regulate metabolism and energy mobilisation for everyday activities (Busch and Hayward 2009), whilst at stress-induced concentrations, they provide an immediate energy supply and induce a cascade of adaptive physiological and behavioural responses (Deak 2007;Sapolsky et al. 2000). ...
Captivity can alter the stress physiology and behaviour of an animal in both the short- and long-term through repetitive exposure to novel stressors and, subsequently, may reduce the success of conservation efforts such as translocation and reintroduction. The Tasmanian devil ( Sarcophilus harrisii ) is threatened with extinction from a fatal facial tumour disease which has led to the establishment of an insurance meta-population designed for future reintroductions of disease-free devils. The meta-population is comprised of intensive captive and free-range captive environments; however, no study has yet examined the long-term physiological implications of captivity on devils. We used non-invasive faecal glucocorticoid metabolite (FGM) monitoring to determine if there were any differences in adrenal activity between intensive captive, free-range captive, and wild devils. FGMs were not age- or sexdependent, and we found that all population-types had similar intra-population variability and mean FGMs. In conclusion, both types of captive environment maintain stress profiles similar to wild devils.
... Acute stress physiologically activates the hypothalamic pituitary adrenal (HPA) axis and the autonomic nervous system (ANS). The chronic activation of HPA results in the increase of adrenocorticotropin hormone (ACTH) and cortisol levels [11]. Meanwhile, the rapid activation of ANS can lead to changes in heart rate, blood pressure, skin temperature, and skin conductivity. ...
Human failures occur in nuclear power plants when operators are under acute stress. Therefore, an automatic stressed recognition system should be developed for nuclear power work. Previous studies on the prediction of stress are limited because of their reliance on subjective ratings and contact physiological measurement. To solve this problem, we developed a non-intrusive way by using voice features to detect stress. We aim to build a system that can estimate the level of stress from speech which may be applied to nuclear power plants where operators engage in regular verbal communication as part of their duties. In this study, we collected voice recordings from 34 participants during a simulated nuclear plant power task in a time-limited situation that requires high cognitive resources. Mel frequency cepstrum coefficients (MFCCs) were extracted from stressed voice samples and the neural network model was used to assess stress levels continuously. The experimental results showed that voice features can provide satisfactory predictions of the stress state. Mean relative errors of prediction are possible within approximately 5%. We discuss the implications of the use of voice as a minimally intrusive means for monitoring the effects of stress on cognitive performance in practical applications.
... The relationship between stress and insomnia is well established and stress is considered a major driving force behind sleep problems (Drake et al., 2014;Morin et al., 2003). Stress is associated with physiological and psychological arousal and release of stress hormones like cortisol and adrenaline (Axelrod & Reisine, 1984). Stress can both impair the individual's physical ability to sleep (e.g., by elevating cortisol levels and disturbing melatonin secretion), and contribute to intrusive thoughts and worrying about stressors (Lovallo & Buchanan, 2017). ...
Insomnia is a growing public health concern and a risk factor for reduced health, safety, and performance among workers. This study investigated and compared the predictive value of personality traits and psychosocial factors associated with symptoms of insomnia. The study followed a longitudinal design and included 206 Norwegian police employees (52% men). The predictors of insomnia symptoms were divided into the following groups in the multiple regression analyses: 1) demands, control, and support at work, 2) stress and overcommitment, and 3) the personality traits of the five-factor model. A fourth final model included significant predictors from the initial analyses. The results showed high stability in insomnia symptoms at baseline and follow-up six months later. Neuroticism was the strongest and most stable predictor of insomnia, and associated with an increase in insomnia symptoms after six months. Overcommitment and stress had positive associations with insomnia symptoms but could not predict changes after six months. Social support had a negative association with insomnia, whereas job demands and control at work had no significant association with insomnia symptoms measured at follow-up six months later. The findings demonstrate that the personality trait neuroticism can play an important role in the development and maintenance of insomnia symptoms. Job demands and resources only explained a marginal proportion of variance in insomnia symptoms measured six months later in police employees, indicating that they may be less crucial in the development of insomnia. However, more research on the potential interaction effects between personality and organizational factors is needed. The study highlights the importance of taking personality characteristics into consideration when investigating predictors of insomnia.
... The body maintains a relatively constant glucose concentration through the synthesis and catabolism of liver glycogen [46]. Previous studies have shown that aquatic animals respond to the stress of low temperatures and transport by breaking down liver glycogen to maintain the body's energy requirements [47,48]. Eugenol has also been found by previous studies to relieve transportation stress, with significantly reduced serum levels of COR (cortisol) and GOT (glutamic oxaloacetic transaminase) found in hybrid amazon catfish (Pseu-doplatystoma reticulatum × Leiarius marmoratus) anesthetized by eugenol [49]. ...
This study investigated the effects of added eugenol on water quality and the metabolism and antioxidant capacity of the liver and gills of the greater amberjack (Seriola dumerili) during simulated transport. The juvenile fish (10.34 ± 1.33 g) were transported in sealed plastic bags containing different eugenol concentrations at a density of 24.79 kg/m3 for 8 h. The different eugenol concentrations were divided into five groups: 0 μL/mL (control group), 0.0125 μL/mL, 0.025 μL/mL, 0.0375 μL/mL, and 0.05 μL/mL, with three replicates of each. The results showed that 0.05 μL/mL of eugenol could significantly increase dissolved oxygen, but 0.025 μL/mL–0.0375 μL/mL resulted in a significant decrease in dissolved oxygen and significant increases in NH4+-N and NO2−-N. It was found that 0.05 μL/mL of eugenol caused significant up-regulation of the relative expression of CPT-1 in the liver, significant down-regulation of the relative expression of FAS and PK in the liver and gills, a significant increase in glycogen concentration, and a significant decrease in glucose concentration. This suggests that 0.05 μL/mL of eugenol could reduce the metabolic capacity of fish. In addition, 0.05 μL/mL of eugenol caused significant up-regulation of the relative expression of CAT and a significant decrease of MDA concentration in the liver. Meanwhile, the gills showed significant up-regulation of CAT relative expression, significant down-regulation of Keap1 relative expression, and a significant increase in GSH activity, resulting in a significant increase in MDA concentration when the concentration of eugenol reached or exceeded 0.025 μL/mL. This suggests that 0.05 μL/mL eugenol could improve the antioxidant capacity of fish and lipid peroxidation levels in the gills. In conclusion, the addition of 0.05 μL/mL eugenol could improve water quality, and the metabolic and antioxidant capacities of liver and gills, but it could also increase lipid peroxidation levels in the gills under transport conditions.
... Eosinophils in the intestinal mucosa contain substance P, vasoactive intestinal peptide, calcitonin gene-related peptide, and corticotropin-releasing hormone (CRH). 32,33 Also known as corticotropin-releasing factor, CRH plays an important role in the stress response 34 and is involved in IBS pathophysiology. 35 The brain-gut axis in IBS patients may have an exaggerated response to CRH. 35 The presence of CRH in intestinal mucosal eosinophils of IBS patients suggests that mucosal eosinophils play a role in IBS pathophysiology. ...
The pathophysiology of irritable bowel syndrome (IBS) has not yet been fully elucidated. We reviewed articles addressing IBS that have been published in the last 2 years and selected papers related to IBS pathophysiology and treatment. Studies of intestinal bacteria, low-grade mucosal inflammation, and increased mucosal permeability—factors involved in the pathophysiology of IBS—have been conducted. In addition, the involvement of intestinal bacteria in IBS pathology has been clarified; many studies of treatments related to intestinal bacteria have been reported. Moreover, several studies address the effect on IBS of antidepressants and psychotherapy through the brain–gut axis. The contents of these papers are described in this narrative review.
... activating the hypothalamic-pituitary-adrenal (HPA) axis and increasing corticosteroid levels. Both systems fight against stress in the body (Axelrod and Reisine 1984). The HPA and sympathoadrenomedullary systems are involved in maintaining the stability of the organism during stress, and the adrenal gland is the final decision-making center in both systems (Petrovic--Kosanovic et al. 2012). ...
In this study, we aimed to investigate the effects of vitamin E on mouse adrenal glands in immobilization stress. Twenty-eight male, 10-week-old, BALB/C mice weighing 30-45 grams were divided into four groups. Mice were placed in a cage where no movement was allowed 6 hours/day for 7 days for immobilization stress. 10 ml/kg vitamin E was administered orogastri-cally 1 hour before immobilization stress in the vitamin E and stress+vitamin E group. At the end of the 7th day, all the animals were subjected to elevated-plus maze (anxiety) and forced swimming (depression) tests. Left adrenal glands were dissected for routine paraffin tissue embedding protocol. Adrenal sections were stained with hematoxylin-eosin and Azan. Malonaldehyde (MDA) levels were also measured in the adrenal tissues. Anxiety level (0.023), depression level (p=0.042) and MDA values (p=0.01) were significantly increased in the stress group. Histological sections of the stress group showed cortical atrophy, medullary hypertrophy, vascular dilation and hemorrhage. Azan staining revealed a thinned capsule and corticomedullary fibrosis in the stress group. Pathologies induced by immobilization stress were mostly reversed after vitamin E administration. The results suggested that vitamin E alleviates adverse effects of immobilization stress (oxidative, behavioral and histopathologic changes) in mice.
... Part of the strength of an online community is that it provides people with similar interests a chance to interact. Potentially, cooperation could be greatly increased as there are more opportunities for interaction (Axelrod, 1984). ...
To date much of the entrepreneurial ecosystems literature treated ecosystems as confined geographic locations with definitive boards. However, in the past decades, technological innovation and developments in social relationships (e.g., online platforms, social media, and the sharing economy) have extended and blurred the boundaries of entrepreneurial ecosystems. Thus, current research on entrepreneurial ecosystems often underestimates the reach and impacts of a given ecosystem. To remedy this, we advocate the use of a more holistic approach in modern entrepreneurial ecosystems frameworks which includes social relationships and technology, thus extending beyond geographical barriers. We discuss how technology has dissolved locational barriers and connected elements of ecosystems, how social relationships maximize advantages through greater resource access, and how the entrepreneurship ecosystem now exists on a plane that is both physical and cyber.
... The decrease in the activity of HPA systems indicates the ability of sheep to adapt to the stress factor and thus points to the emergence of an adaptation process. This can be explained by the negative feedback mechanism between the adrenal cortex and the hypothalamus (CRH) and between argininevasopressin (AVP) and the pituitary (ACTH) (Axelrod et al., 1984, Buckingham, 2006Harno et al., 2010). ...
The aim of this study was to estimate rate of cortisol release from ewe’s adrenal gland cortex and medulla tissue and the participation 11β-HSD1 and 2 in modulating adrenal glucocorticosteroids release, determine the expression size of these two isoforms in both parts of adrenal glands after single and repeated stress (3 times every 24h), when adaptive processes take place. The experiment was carried on 15 ewes, outside the breeding season. The research material consisted of adrenal glands obtained from control sheep (CON), sheep subjected to one-hour individual isolation from the herd (S1) and three times repeated stress factor at one-day intervals (S2). Immediately after slaughter, the adrenal glands from each sheep were placed on ice in 0.9% NaCl, then they were cut into smaller sections of similar weight (approx. 50 mg), covering the cortical and medullary layers of the adrenal glands. Sections of obtained tissues were weighed and placed in incubation wells (Sigma cell culture) containing 1 ml of incubation Eagle's medium with the addition of bovine albumin (BSA, 50 mg / 100 ml). Tissue incubation was carried out in an atmosphere of carbogen - 95% O2 and 5% CO2 at 38oC in a Sanyo incubator (MCO-18AIC). After 10 minutes of stabilization, the sections of core and adrenal cortex tissue were transferred to subsequent wells containing pure Eagle Medium. The same section was transferred to consecutive incubation wells containing clean incubation medium every 30 minutes. The medium harvested from the wells after 30, 60 and 90 minutes of incubation of adrenal tissue was frozen until the scheduled cortisol concentration de-termination by RIA (Orion Diagnostica) was performed. Another pieces of tissue the cortex and adrenal medulla from each sheep immediately placed in the RNAlater. Measurements of the gene expression of 11β-HSD1 and 2 expression in the adrenal cortex and medulla were performed using Real-time qPCR method. Starters and TaqMan MGB probes were designed by Applied Biosystem. In the conducted in vitro experiment, a significant reduction in the amount of cortisol released from adrenal cortex tissue into the medium after single stress factor was found, from 3.27 ± 0.69 pg･mg-1 tissue after first 30 minutes of experiment to 0.70 ± 0.15 pg･mg-1 of tissue after 90 minutes (P < 0.01). A similar profile of cortisol release from the adrenal cortex tissue was found in control sheep (P > 0.05). Experimental Group 2 (S2) had a similar profile of cortisol release during the all-time of incubation, however the values found were always lower than those observed in the control and single stress sheep Experimental Group 1 (S1) (1.34 ± 0.37 to 0.30 ± 0.08 pg･mg-1 of tissue; P < 0.05). After repeated stress, incubation of adrenal cortex tissue showed a similar profile of changes in cortisol release, however the values were significantly lower than those found in the singly stressed animals (from 1.30 ± 0.37 pg･mg-1 after 30 minutes to 0.27 ± 0.08 pg･mg-1 tissue after 90 minutes; P < 0.01). Incubation of adrenal medulla tissue obtained from singly stressed animals showed cortisol release to the medium much lower in comparison to adrenal cortex layer, however constant during the whole incubation time, value 1.04 ± 0.36 pg/mg-1 tissue noted after first 30 minutes to 0.77 ± 0.06 pg･mg-1 after 90 minutes of experiment; P > 0.05). When the stress factor was repeated three times, the amount of cortisol released was like that observed in the control secretion; P > 0.05). Analysis of 11β-HSD 1 expression in adrenal cortex tissue from singly stressed sheep showed an over threefold increase (350 ± 25 RQ), while measurement after stress factor was repeated three times demonstrated increase, however the value turned out to be two times lower than after a single stress (160 ± 35 RQ). The expression value of 11β-HSD 2 in the adrenal cortex tissue showed a significant reduction after both single (15 ± 7 RQ and repeated stress (22 ± 3.0 RQ). No significant differences were found in the expression value of this enzyme in the sheep adrenal medulla in both experimental groups in comparison to control group (P > 0.05). The obtained results indicate the immanent abilities of the adrenal glands, probably to a certain extent, to control the release of cortisol, conditioned by the presence and variable activity of the enzyme 11β-HSD, particularly isoform 1, in adrenal glands without the need to activate all HPA axis structures during stress and adaptation processes.
... Changes in hormone levels mediate changes in leaf morphology, and stress environment will induce changes in plant hormone balance [60]. Under salt stress, the auxin homeostasis and distribution pattern of Arabidopsis thaliana change, which will inhibit its lateral root germination and organogenesis [61]. ...
Salt stress inhibited the growth of maize. B46 and NC236 were chosen as materials and NaCl concentrations (0, 55, 110, 165, and 220 mmol L−1) were set. We found the activities of SOD, POD, CAT, APX, GR, MDHAR, and DHAR decreased under NaCl stress. Compared with NC236, the contents of AsA and GSH, AsA/DHA and GSH/GSSG of B46 decreased. The content of O2−, H2O2, MDA, and EL of B46 increased. The contents of NO3− and NO2− decreased, while the content of NH4+ increased under high NaCl concentration. The activities of NR and NiR decreased, while the activities of GS and GOGAT increased first and then decreased. For B46 and NC236, the maximum of NADH-GDH and NAD-GDH appeared at 165 and 110 mmol L−1 NaCl concentration, respectively. Compared with B46, and the GOT and GPT activities of NC236 increased first and then decreased. With the increase of NaCl concentration, the contents of proline, soluble protein, and soluble sugar were increased. The Na+ content of B46 and NC236 increased, and the K+ content and K+/Na+ decreased. Compared with NC236, B46 had higher IAA content in leaf, higher Z + ZR content in leaf and root, and lower ABA content in leaf and root.
The quality of our relationships with other species, as predators, prey, companions, and subjects of curiosity or research, profits from our being ethologically informed. This chapter explores several dimensions of these relationships along with comments on the importance of an ethological attitude and ethologically informed design in pursuit of a better understanding of how best to behave as responsible stewards and students of other species. Design, in the sense of a coherent program that guides our practice, involves identifying and defining the traits that appear important to us, as well as the ways in which we manipulate, observe, measure, and interpret them. Design both guides and is guided by the questions or problems we wish to address. To be ethologically informed, a design implicitly acknowledges four key biological perspectives, identified in the earliest conceptual beginnings of ethology. Each perspective reflects different temporal and spatial orientations and levels of organisation, but all are profoundly involved in the causation of behaviour; they are developmental, ecological, evolutionary, and physiological (DEEP). This integrative biology in concert with an ethological attitude, emphasising freedom from implicit bias, is a valuable approach to all forms of captive animal management as well as research design. Such an approach will reveal connections within and between our subjects and ourselves that are of both great intrinsic interest and generalisable utility in solving problems that we all share.
Successful reproduction is a cornerstone in food animal industry in order to sustain food production for human. Therefore, various methods focusing on genetics and postnatal environment have been identified and applied to improve fertility in livestock. Yet there is evidence indicating that environmental factors during prenatal and/or neonatal life can also impact the function of reproductive system and fertility in the animals during adulthood, which is called the developmental programming of reproduction. The current review summarizes data associated with the developmental origins of reproduction in the female animals. In this regard, this review focuses on the effect of plane of nutrition, maternal body condition, hypoxia, litter size, maternal age and parity, level of milk production and milk components, lactocrine signaling, stress, thermal stress, exposure to androgens, endocrine disrupting chemicals, mycotoxins and pollutants, affliction with infection and inflammation, and maternal gut microbiota during prenatal and neonatal periods on the neuroendocrine system, puberty, health of reproductive organs and fertility in the female offspring. It is noteworthy that these prenatal and neonatal factors do not always exert their effects on the reproductive performance of the female by compromising the development of organs directly related to reproductive function such as hypothalamus, pituitary, ovary, oviduct and uterus. Since they can impair the development of non-reproductive organs and systems modulating reproductive function as well (e.g., metabolic system and level of milk yield in dairy animals). Furthermore, when these factors affect the epigenetics of the offspring, their adverse effects will not be limited to one generation and can transfer transgenerationally. Hence, pinpointing the factors influencing developmental programming of reproduction and considering them in management of livestock operations could be a potential strategy to help improve fertility in food animals.
The memory loss associated with increased oxidative stress due to increased level of free radicals. Oxidative stress has been involved in several diseases includes cancer, atherosclerosis and neurodegenerative diseases.This study aimed to estimate the correlation of antioxidant and antistress activity with nootropic activity of aqueous extract of pomegranate (Punica granatum) by in-vivo noninvasive studies using rats. The in-vitro antioxidant activity was determined based on the ability of the Punica granatum to scavenge free radicals and lipid peroxidation inhibiting activity. The antistress effect of the aqueous extract of Punica granatum for 24h treatment (100 and 300mg/kg, p.o.) was evaluated by using the forced swim stress test in rats. The 24h urinary excretion of vanillylmandellic acid (VMA), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and ascorbic acid (AA) was determined in all groups under normal and stressed conditions by HPLC and spectrophotometric methods in all groups, were selected as noninvasive biomarkers. Nootropic activity activities of Punica granatum fruit extract were estimated as locomotor and working memory in rats in a Y-maze apparatus. Administration of aqueous extract of Punica granatum at a dose of 100 and 300mg/kg reduced the urinary metabolite levels. Punica granatum treatment showed significant dose dependent variation in non-invasive biomarker levels in urine samples of rats taken after 24h. The treatment with Punica granatum extracts improved the percentage entry of rats into safer zone, it means acquisition (learning) retention and retrieval (memory) were improved in rats compared to stress controls. Cognition determined by working memory and locomotor activity results were shown to be dose-dependent. The results of this study strongly suggestedantioxidant, antistress and nootropic activity effect of Punica granatumin rodents were correlated. The data obtained were analyzed by one-way ANOVA followed bytukey test. p<0.05 was considered to be significant. There is substantial evidence that flavonoids play an active role in providing antioxidant, antistress and nootropic activities of Punica granatum extracts. The findings of the present investigations indicate that the Punica granatum has significant antistress activity, which may be due to the immunostimulating property and increased resistance, nonspecifically, against all experimental stress conditions. The study provided scientific evidence for their utility as nootropic agents and to advocate their use in foods.
Transport conditions have the potential to alter the physiological responses of animals to the psychological or physical stress of transport. Transportation may introduce multiple physical and psychological stressors to unweaned calves and adult cattle, including noise, overcrowding, food and water deprivation, extreme temperatures, commingling with unfamiliar animals, handling by unfamiliar humans, and being placed in a novel environment upon arrival. Apart from these factors, the type of road and even driving skill may affect the welfare of animals. One of the concerns regarding cattle transport is that the handling and marketing of animals prior to a journey may lengthen the period of feed withdrawal. Furthermore, feed withdrawal can impact animal welfare through hunger and metabolic stress. Transportation is also associated with a decrease in animal performance as well as an increase in the incidence of bovine respiratory disease. It is well established that the transportation of cattle is a stressor that causes a quantifiable response; however, excessive stress during transport resulting in physiological or pathological changes can be reduced with best management practices. The objective of this review was to analyse the available scientific literature pertaining to the transport by road of cattle, including unweaned calves.
Ovarian aging is a complex process influenced by multiple factors, such as age, genetics, neuroendocrine, social psychology, environment, and behavior. Understanding the risk factors of ovarian aging is essential for delaying or preventing ovarian aging, which can improve a woman’s quality of life and happiness and considerably reduce the medical burden. This chapter expounds on the influence of these critical factors on ovarian function.
Copper is widely used in agriculture and aquaculture due to its high disinfection properties and relatively low cost. However, the increase in copper concentration due to evaporation can lead to water reservoir pollution, which can harm the health of consumers. The present study aimed to determine the role of sulfated polysaccharides (SPs) extracted from Sargassum tenerimum algae in reducing lesions caused by the heavy metal copper. Zebrafish (Danio rerio) were used as a human model in five treatments. The negative and positive control groups were fed a diet containing zero percent of SPs, while the experimental groups were fed 0.5%, 1%, and 1.5% of SPs in three treatments for 56 days, finally CuSO4 was exposed only to the positive control group and the groups fed with SPs. Results showed a significant decrease in the activity level of ALT enzymes (39–16 U/mL), AST (67–46 U/mL), and ALP (485–237 U/mL), confirming the results obtained from histopathological studies in CuSO4 exposed groups. The addition of SPs to the diet resulted in a significant reduction (sig < 0.05) of mortalities due to the decrease of tissue damage. Additionally, due to the anti-inflammatory properties and the protective effect of SPs, a significant decrease (sig < 0.05) was observed in the relative expression of Il-1β and Tnf-α genes.
The purpose of this 2006 book is to present non-invasive methods of measuring the biological responses to psychosocial stress in humans, in non-laboratory (field) settings. Following the pathways of Seyle's General Adaptation Syndrome, the text first describes how to assess the psychosocial stressors of everyday life and then outlines how to measure the psychological, behavioral, neurohumeral, physiological and immunological responses to them. The book concludes with practical information on assessing special populations, analyzing the often-complicated data that are collected in field stress studies and the ethical treatment of human subjects in stress studies. It is intended to be a practical guide for developing and conducting psychophysiological stress research in human biology. This book will assist students and professionals in designing field studies of stress.
The purpose of this 2006 book is to present non-invasive methods of measuring the biological responses to psychosocial stress in humans, in non-laboratory (field) settings. Following the pathways of Seyle's General Adaptation Syndrome, the text first describes how to assess the psychosocial stressors of everyday life and then outlines how to measure the psychological, behavioral, neurohumeral, physiological and immunological responses to them. The book concludes with practical information on assessing special populations, analyzing the often-complicated data that are collected in field stress studies and the ethical treatment of human subjects in stress studies. It is intended to be a practical guide for developing and conducting psychophysiological stress research in human biology. This book will assist students and professionals in designing field studies of stress.
The purpose of this 2006 book is to present non-invasive methods of measuring the biological responses to psychosocial stress in humans, in non-laboratory (field) settings. Following the pathways of Seyle's General Adaptation Syndrome, the text first describes how to assess the psychosocial stressors of everyday life and then outlines how to measure the psychological, behavioral, neurohumeral, physiological and immunological responses to them. The book concludes with practical information on assessing special populations, analyzing the often-complicated data that are collected in field stress studies and the ethical treatment of human subjects in stress studies. It is intended to be a practical guide for developing and conducting psychophysiological stress research in human biology. This book will assist students and professionals in designing field studies of stress.
The purpose of this 2006 book is to present non-invasive methods of measuring the biological responses to psychosocial stress in humans, in non-laboratory (field) settings. Following the pathways of Seyle's General Adaptation Syndrome, the text first describes how to assess the psychosocial stressors of everyday life and then outlines how to measure the psychological, behavioral, neurohumeral, physiological and immunological responses to them. The book concludes with practical information on assessing special populations, analyzing the often-complicated data that are collected in field stress studies and the ethical treatment of human subjects in stress studies. It is intended to be a practical guide for developing and conducting psychophysiological stress research in human biology. This book will assist students and professionals in designing field studies of stress.
The purpose of this 2006 book is to present non-invasive methods of measuring the biological responses to psychosocial stress in humans, in non-laboratory (field) settings. Following the pathways of Seyle's General Adaptation Syndrome, the text first describes how to assess the psychosocial stressors of everyday life and then outlines how to measure the psychological, behavioral, neurohumeral, physiological and immunological responses to them. The book concludes with practical information on assessing special populations, analyzing the often-complicated data that are collected in field stress studies and the ethical treatment of human subjects in stress studies. It is intended to be a practical guide for developing and conducting psychophysiological stress research in human biology. This book will assist students and professionals in designing field studies of stress.
The purpose of this 2006 book is to present non-invasive methods of measuring the biological responses to psychosocial stress in humans, in non-laboratory (field) settings. Following the pathways of Seyle's General Adaptation Syndrome, the text first describes how to assess the psychosocial stressors of everyday life and then outlines how to measure the psychological, behavioral, neurohumeral, physiological and immunological responses to them. The book concludes with practical information on assessing special populations, analyzing the often-complicated data that are collected in field stress studies and the ethical treatment of human subjects in stress studies. It is intended to be a practical guide for developing and conducting psychophysiological stress research in human biology. This book will assist students and professionals in designing field studies of stress.
The purpose of this 2006 book is to present non-invasive methods of measuring the biological responses to psychosocial stress in humans, in non-laboratory (field) settings. Following the pathways of Seyle's General Adaptation Syndrome, the text first describes how to assess the psychosocial stressors of everyday life and then outlines how to measure the psychological, behavioral, neurohumeral, physiological and immunological responses to them. The book concludes with practical information on assessing special populations, analyzing the often-complicated data that are collected in field stress studies and the ethical treatment of human subjects in stress studies. It is intended to be a practical guide for developing and conducting psychophysiological stress research in human biology. This book will assist students and professionals in designing field studies of stress.
The purpose of this 2006 book is to present non-invasive methods of measuring the biological responses to psychosocial stress in humans, in non-laboratory (field) settings. Following the pathways of Seyle's General Adaptation Syndrome, the text first describes how to assess the psychosocial stressors of everyday life and then outlines how to measure the psychological, behavioral, neurohumeral, physiological and immunological responses to them. The book concludes with practical information on assessing special populations, analyzing the often-complicated data that are collected in field stress studies and the ethical treatment of human subjects in stress studies. It is intended to be a practical guide for developing and conducting psychophysiological stress research in human biology. This book will assist students and professionals in designing field studies of stress.
The purpose of this 2006 book is to present non-invasive methods of measuring the biological responses to psychosocial stress in humans, in non-laboratory (field) settings. Following the pathways of Seyle's General Adaptation Syndrome, the text first describes how to assess the psychosocial stressors of everyday life and then outlines how to measure the psychological, behavioral, neurohumeral, physiological and immunological responses to them. The book concludes with practical information on assessing special populations, analyzing the often-complicated data that are collected in field stress studies and the ethical treatment of human subjects in stress studies. It is intended to be a practical guide for developing and conducting psychophysiological stress research in human biology. This book will assist students and professionals in designing field studies of stress.
The purpose of this 2006 book is to present non-invasive methods of measuring the biological responses to psychosocial stress in humans, in non-laboratory (field) settings. Following the pathways of Seyle's General Adaptation Syndrome, the text first describes how to assess the psychosocial stressors of everyday life and then outlines how to measure the psychological, behavioral, neurohumeral, physiological and immunological responses to them. The book concludes with practical information on assessing special populations, analyzing the often-complicated data that are collected in field stress studies and the ethical treatment of human subjects in stress studies. It is intended to be a practical guide for developing and conducting psychophysiological stress research in human biology. This book will assist students and professionals in designing field studies of stress.
The purpose of this 2006 book is to present non-invasive methods of measuring the biological responses to psychosocial stress in humans, in non-laboratory (field) settings. Following the pathways of Seyle's General Adaptation Syndrome, the text first describes how to assess the psychosocial stressors of everyday life and then outlines how to measure the psychological, behavioral, neurohumeral, physiological and immunological responses to them. The book concludes with practical information on assessing special populations, analyzing the often-complicated data that are collected in field stress studies and the ethical treatment of human subjects in stress studies. It is intended to be a practical guide for developing and conducting psychophysiological stress research in human biology. This book will assist students and professionals in designing field studies of stress.
Termografía infrarroja como herramienta de valoración del estrés en conejos
Background/Aims
The psycho-immune-neuroendocrine (PINE) network is a predominantly physiological (metabolomic) model constructed from the literature, inter-linking multiple biological processes associated with major depressive disorder (MDD), thereby integrating putative mechanistic pathways for MDD into a single network.
Material and methods
Previously published metabolomic pathways for the PINE network based on literature searches conducted in 1991–2021 were used to construct an edge table summarizing all physiological pathways in pairs of origin nodes and target nodes. The Gephi software program was used to calculate network metrics from the edge table, including total degree and centrality measures, to ascertain key network nodes and construct a directed network graph.
Results
An edge table and directional network graph of physiological relationships in the PINE network is presented. The network has properties consistent with complex biological systems, with analysis yielding key network nodes comprising pro-inflammatory cytokines (TNF- α, IL6 and IL1), glucocorticoids and corticotropin releasing hormone (CRH). These may represent central structural and regulatory elements in the context of MDD.
Conclusion
The identified hubs have a high degree of connection and are known to play roles in the progression from health to MDD. These nodes represent strategic targets for therapeutic intervention or prevention. Future work is required to build a weighted and dynamic simulation of the network PINE.
Objectives
Although cold exposure is commonly believed to be causally related to acute viral respiratory infections, its effect on the immune system is largely unexplored. In this study, we determined transcript levels of a large panel of immune genes in blood before and after cold exposure. We included both Dutch Europid and Dutch South Asian men to address whether the immune system is differently regulated in the metabolically vulnerable South Asian population.
Methods
Fasted blood samples were obtained from nonobese Dutch Europid (n = 11; mean age 26 ± 3 y) and Dutch South Asian (n = 12; mean age 28 ± 3 y) men before and directly after short-term (∼2.5 h) mild cold exposure. Transcript levels of 144 immune genes were measured using a dual-color reverse transcriptase multiplex ligation-dependent probe amplification (dcRT-MLPA) assay.
Results
Cold exposure acutely upregulated mRNA levels of GNLY (+35%, P < 0.001) and PRF1 (+45%, P < 0.001), which encode cytotoxic proteins, and CCL4 (+8%, P < 0.01) and CCL5 (+5%, P < 0.05), both pro-inflammatory chemokines. At thermoneutrality, mRNA levels of four markers of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR)-family, involved in inflammasomes, were lower in Dutch South Asians compared to Dutch Europids, namely NLRP2 (−57%, P < 0.05), NLRP7 (−17%, P < 0.05), NLRP10 (−21%, P < 0.05), and NLRC4 (−23%, P < 0.05).
Conclusions
Mild cold exposure acutely increases mRNA levels of genes involved in cytotoxicity of immune cells in blood. In addition, Dutch South Asians display lower circulating mRNA levels of inflammasome genes compared to Dutch Europids.
A double antibody immunoprecipitation technique using affinity-purified adrenocorticotropic hormone (ACTH) antiserum was employed to investigate the biosynthesis of ACTH in a mouse pituitary tumor cell line. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of cell extracts resolved four forms of ACTH with apparent molecular weights of 4,500, 13,000, 23,000, and 31,000. These four forms of ACTH can be detected by radioimmunoassay of cell extracts or by immunoprecipitation of cell extracts following incubation of cultures in [3H] tryptophan, [3H] lysine, or [3H] tyrosine. The double antibody immunoprecipitation scheme developed is specific, quantitative, and reproducible. ACTH biosynthesis was examined in both steady and pulse-labeling experiments using [8H] tyrosine or [3H] lysine. The results of these experiments are consistent with the proposal that Mr=31,000 ACTH is the biosynthetic precursor for all three smaller forms of ACTH and that Mr=23,000 ACTH is a biosynthetic intermediate. Both Mr=13,000 ACTH and Mr=4,500 ACTH are derived from the intracellular processing of Mr=31,000 ACTH.
Incubation of human astrocytoma cells (1321N1) with low concentrations of isoproterenol results in a specific loss of responsiveness to catecholamines as evidenced by a decreased accumulation of cAMP in intact cells, a reduction in isoproterenol-stimulated adenylate cyclase activity, and a decrease in beta-adrenergic receptor density, as measured by the specific binding of 125I-hydroxybenzylpindolol. The kinetics of desensitization suggest the involvement of two different reactions. The initial reaction involves a rapid loss of adenylate cyclase activity with little loss of beta-adrenergic receptors. Subsequently, a slower reaction results in the loss of measurable beta-adrenergic receptors. The degree of loss of both parameters was similar after 24 h of desensitization. It is concluded that the loss of beta-adrenergic receptors is an event that occurs as a result of the initial uncoupling of the beta-receptor-linked adenylate cyclase.
Rat adrenal gland levels of dopamine beta-hydroxylase are subject to dual control. Activation of the splanchnic nerves to the adrenal medulla by reserpine induces the synthesis of dopamine beta-hydroxylase without altering the rate of enzyme degradation. In contrast, hypophysectomy causes a decline in steady state dopamine beta-hydroxylase levels by first accelerating the rate of degradation, then by slowing the rate of enzyme synthesis as well. Adrenocorticotropic hormone administration partially reversed the effect of hypophysectomy on dopamin beta-hydroxylase degradation. These findings suggest that the trans-synaptic factors controlling dopamine beta-hydroxylase induction act by a different mechanism (enzyme synthesis) than the hormonal controls regulating steady state levels (enzyme degradation). Thus, active inhibition of enzyme degradation may be an important control in maintenance of steady state enzyme levels.
The properties of the beta-adrenergic receptor which regulates adenylate cyclase [ATP pyrophosphate-lyase (cyclizing)8 EC 4.6.1.1] in the pineal gland are similar to the properties of the sites which specifically bind l-[3H]alprenolol, a potent beta-adrenergic antagonist. Stimulation of the beta-adrenergic receptor results in a 30-fold increase in the activity of N-acetyltransferase (= arylamine acetyltransferase; acetyl CoA:arylamine N-acetyltransferase, EC 2.3.1.5), an enzyme involved in the synthesis of thepineal hormone melatonin. In the normal diurnal light-dark cycle there is greater physiological stimulation of the beta-adrenergic receptor in the pineal during the night than during the day. Pineals from rats kept in constant light for 24 hr possess more hormone-sensitive adenylate cyclase and specifically bind more l-[3H]alprenolol than do pineals from rats kept in the dark overnight. When rats, exposed to light for 24 hr, are treated with the beat-adrenergic agonist isoproterenol, there is a rapid loss of both hormone-sensitive adenylate cyclase activity and specific l-[3H]alprenolol binding sites. There is no change in the affinity of adenylate cyclase for isoproterenol or for its substrate, ATP. Similarly, although there are fewer binding sites, there is no change in the affinity of the remaining sites for either agonist or antagonist. Inhibition of protein synthesis with cycloheximide does not affect the loss of either adenylate cyclase activity or specific binding sites. The data suggest that stimulation of the beta-adrenergic receptor causes a rapid decrease in the number of available receptors and in hormone-sensitive adenylate cyclase activity; conversely, lack of stimulation causes an increase in these parameters. It is suggested that these changes contribute to the phenomena of super- and subsensitivity in the pineal gland by regulating the capacity of the pineal to synthesize cyclic AMP in response to beta-adrenergic stimulation.
The activity of phenylethanolamine N-methyltransferase, the enzyme that catalyzes the N-methylation of noradrenaline to form adrenaline, falls following hypophysectomy. Enzyme activity can be restored by injections of adrenocorticotropic hormone (ACTH) or of dexamethasone, a potent synthetic glucocorticoid. The effect of ACTH on the adrenaline-forming enzyme is not direct, but involves stimulation of the release of endogenous glucocorticoids from the adrenal cortex. These steroids then act to elevate the activity of the transferase, which is principally localized in the adrenal medulla. The stimulation by glucocorticoids of phenylethanolamine N-methyltransferase activity can be blocked by the concurrent administration of puromycin or actinomycin D. Glucocorticoids do not stimulate the activity of other adrenal enzymes involved in catecholamine biosynthesis or metabolism, such as tyrosine hydroxylase, catechol O-methyltransferase, or monoamine oxidase.
The development of a sensitive and specific enzymatic assay for dopamine-beta-hydroxylase has enabled us to measure the activity of this enzyme in several tissues where it has previously been measured. The administration of reserpine leads to an increase in dopamine-beta-hydroxylase activity in the rat adrenal, heart, salivary gland, and in sympathetic ganglia. The increase in the heart is preceded by a small but significant fall. We have confirmed the increase in tyrosine hydroxylase which follows the administration of reserpine and have found that the activity of phenylethanolamine-N-methyltransferase also increases after administration of this drug. The activities of two enzymes not involved in the synthesis of catecholamines, monoamine oxidase and lactate dehydrogenase, are not affected by reserpine treatment. The rise of dopamine-beta-hydroxylase activity in the sympathetic ganglia is blocked by surgical decentralization.
A technique was devised to monitor plasma catecholamines in a minimally obtrusive fashion in subjects going about their working activities. There was a disparity between plasma norepinephrine and epinephrine levels in different situations. During public speaking, epinephrine levels increase twofold, whereas during physical exercise, norepinephrine levels increase threefold. It seemed that while exercise induces a response of the sympathetic nervous system, psychological stress induces primarily an adrenal response.
(JAMA 243:340-342, 1980)
The distribution of chromaffin tissue in the rabbit, frog and dogfish is described and compared with findings previously reported for the human foetus. The results are correlated with the adrenaline-noradrenaline content of the tissues.
It is shown that in the dogfish, where the chromaffin tissue is completely separate from adrenocortical material, the pressor activity of the tissue is entirely due to noradrenaline. In man and rabbit the intra-adrenal chromaffin tissue contains a mixture of adrenaline and noradrenaline, whilst the pressor activity of the extra-adrenal chromaffin tissue (para-aortic bodies) is entirely due to noradrenaline.
The para-aortic bodies of the human foetus are probably endocrine organs and may be concerned with the humoral control of vasomotor tone.
A 41-residue peptide purified as a corticotropin-releasing factor/beta-endorphin-releasing factor (CRF) in vitro was tested for its ability to stimulate the secretion of ACTH, beta-endorphin, and corticosterone in three animal groups: 1) unanesthesized rats bearing indwelling venous cannulae, 2) rats pretreated with chloropromazine plus morphine sulfate plus pentobarbital (CPZ-MS-Nb, and 3) rats with hypothalamic deafferentiations in the frontal and lateral retrochiasmatic areas. In all three bioassays iv administration of 0.1-10 micrograms CRF elicited a dose-related increase in plasma ACTH and beta-endorphin values over a 5- to 15-min period. Corticosterone secretion was also elevated but responded maximally with all doses of CRF tested. Pretreatment of CPZ-MS-Nb animals with 20 micrograms dexamethasone 4 h before assay abolished the CRF-induced hormone secretion. These data suggest that CRF may play a physiological role in the regulation of the hypothalamic-pituitary-adrenal axis.
Infusion of I-isoproterenol in anesthetised rats induced a dose-dependent increase of the plasma levels of immunoreactive α-MSH (α-MSHi), β-endorphin (β-ENDi), ACTH (ACTHi) and of corticosterone (B). Steady state levels of all of these substances were reached within 20 min after the start of the infusion. The ED50 values of I-isoproterenol for the increase of plasma α-MSHi, β-ENDi, ACTHi and B were similar (42, 86, 84 and 48 ng/kg. min, respectively). Infusion of I-epinephrine also induced a dose-dependent increase of plasma α-MSHi, β-ENDi, ACTHi and B with similar ED50 values (89, III, 110 and 46 ng/kg. min, respectively). The I-epinephrine-induced increase of plasma α-MSHi, β-ENDi, ACTHi and B was blocked by I-propranolol but not by d-propranolol.Pretreatment of rats with dexamethasone (2.0 mg/kg s.c., 16 hr) completely prevented the I-epinephrine-induced increase of plasma ACTHi and B, without affecting the increase of plasma α-MSHi and β-ENDi.We conclude that catecholamines can stimulate the secretion of peptides from the intermediate lobe (e.g. α-MSH, β-END) as well as from the anterior lobe (e.g. ACTH) of the pituitary gland via interaction with one or more β-adrenergic receptor mechanisms.
With the help of immunohistochemical studies using antibodies against bovine adrenal phenylethanolamine-N-methyltransferase (PNMT), the enzyme converting noradrenaline (NA) to adrenaline (A), the cellular localization of PNMT in the rat central nervous system has been demonstrated.The brains were fixed by perfusion with ice cold 4% formalin and sectioned on a cryostat, after which the sections were stained using the indirect immunofluorescence technique. Preimmune serum and PNMT antiserum adsorbed with PNMT served as control sera.Specific immunofluorescence was localized in two groups of reticular nerve cell bodies in the medulla oblongata and in nerve terminals in special nuclei of the brain stem and the spinal cord. A PNMT positive axon bundle was also observed in the reticular formation of the pons-medulla oblongata. The distribution and morphology of these PNMT containing neurons was such that they probably are identical with some catecholamine nerve terminals and cell bodies previously demonstrated with the Falck-Hillarp technique (see Dahlstro¨m and Fuxe18). The hypothesis is therefore given that the PNMT containing neurons represent A containing neurons, and that A may act as a neurotransmitter in the rat brain.The reticular A neurons appear to have similar morphological characteristics as the NA neurons with long ascending and descending fibers to the brain stem and spinal cord. The A terminals are mainly found in certain visceral afferent and efferent nuclei of the lower brain stem, in the locus coeruleus, in certain nuclei or the hypothalamus and in the periventricular grey. The well defined distribution of the A networks to these nuclei underline the view that the A neuron may participate in the control of oxytocin secretion, food and water intake, body temperature, gonadotrophin secretion, blood pressure and respiration and sleep and wakefulness.
A peptide with high potency and intrinsic activity for stimulating the
secretion of corticotropin-like and β -endorphin-like
immunoactivities by cultured anterior pituitary cells has been purified
from ovine hypothalamic extracts. The primary structure of this
41-residue corticotropin- and β -endorphin-releasing factor has
been determined to be:
H-Ser-Gln-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-
Val-Leu-Glu-Met-Thr-Lys-Ala-Asp-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-
Lys-Leu-Leu-Asp-Ile-Ala-NH2 The synthetic peptide is active
in vitro and in vivo.
Adenylyl cyclases are under positive and negative control by guanine nucleotides and hormones1–3. Stimulatory responses are mediated by a guanine nucleotide- and Mg-binding regulatory component4–6 (Ns), a protein that has been purified to homogeneity7–9. Inhibitory responses have been hypothesized1–3,10,11 to be mediated by an analogous regulatory component (Ni) distinct from Ns, but definitive proof for this is lacking and these effects may result from modulation of Ns activity. Recently, Bordetella pertussis toxin has been shown12 to ADP-ribosylate a peptide that is not part of Ns, and this coincides with attenuation of hormonal inhibition of adenylyl cyclase12–17. We show here that cyc
− S49 cells contain a substrate for ADP-ribosylation by pertussis toxin and that the toxin alters GTP dependent inhibition of cyc
− adenyl cyclase activity18. As cyc
− S49 cells do not contain Ns by several criteria5,19–24, we conclude that Ni is a distinct and separate regulatory component of adenylyl cyclase.
Plasma catecholamine concentrations (PCA) were measured during standing and exercise using a precise and sensitive double-isotope derivative technique. By plotting the increase in PCA in the standing position on the y-axis of a coordinate system against the increase in pulse rate, PCA was resolved into two components: one corresponding to the intercept of the y-axis where rise in pulse rate equals zero (CAP) while the other (CAH) was calculated by multiplying the slope of the regression line by the mean increase in pulse rate.–The rise in PCA, mainly noradrenaline, was considerably less during light to moderate exercise than during standing. Thus there was no rise in PCA during exercise until the increase in pulse rate exceeded approximately 30 beats/min and there was no rise in the CAP component during exercise. When PCA began to rise during exercise the increase in PCA per increment in pulse rate was similar to that observed in the standing experiments. There was no difference between the increments in PCA observed during exercise in the supine and the sitting positions but resting PCA was doubled in the sitting position.–It is suggested that 1. the initial rise in pulse rate during exercise is due to withdrawal of parasympathetic activity on the heart 2. the increase adrenergic in vasoconstrictor activity is considerably less during moderate exercise than during standing 3. the increase in plasma noradrenaline during moderate exercise is of cardiac origin.
We have compared the effects of electric foot shock in unhandled rats with those observed in rats previously exposed to repeated
shock sessions. Acute electric shock causes a decrease in the concentration of norepinephrine in the brain. We have found,
however, that prior shock experience modifies the physiological response of the rat to electric stimuli such that subsequent
shock causes a smaller net depletion of brain norepinephrine. This effect is long-lasting and is associated with a decrease
in the lethality of electric foot shock.
Die Effekte von Elektroschocks an den Pfoten von Ratten, die zuvor nie solche Schocks erlitten, wurden mit denen bei Ratten,
die vorher mehrmals diese Art von Schock hatten erleiden müssen, verglichen. Es zeigt sich, daß akute Schockbehandlung eine
Herabsetzung der Noradrenalinkonzentration im Gehirn zur Folge hat. Weiter konnte festgestellt werden, daß Schockerfahrung
die physiologische Reaktion der Ratte auf Elektroschock ändert, und zwar so, daß wiederholte Schocks eine geringfügigere Erniedrigung
der Noradrenalinkonzentration im Gehirn bewirken. Dieser Effekt bleibt während einer längeren Zeit bestehen und ist mit einer
Herabsetzung der Letalität nach Elektroschock an der Rattenpfote verbunden.
The sensitive specific radioenzymatic procedure for determination of catecholamines originally described from our laboratory by Coyle and Henry (1) has been optimized for use in assay of human plasma levels of dopamine, norepinephrine and epinephrine. Dopamine and the total of norepinephrine and epinephrine are assayed by 0-methylation while norepinephrine is determined by N-methylation. Epinephrine is calculated from the difference between the 0-methylation and N-methylation procedures. In a group of 13 normal subjects, plasma levels of epinephrine were found to be 67 ± 9.2 pg/ml, norepinephrine 208 ± 16.9 pg/ml and dopamine 33 ± 8.1 pg/ml. Dopamine determinations are of low reliability because of relatively high blanks and necessary corrections.
Antibodies to synthetic ovine corticotropin releasing factor (CRF) were used to localize nerve fibers and cell bodies in rat brain. Cell bodies, located nera the paraventricular nucleus, send a rich fiber plexus to the median eminence and less dense fiber connections to other hypothalamic and midbrain targets.
Twelve chronically anxious psychiatric out‐patients, comprising six with somatic anxiety and six with psychic anxiety, were treated with (±)‐propranolol, diazepam and placebo for one week each in flexible dosage using a balanced cross‐over experimental design.
After each treatment, in addition to ratings completed by patient and psychiatrist, finger tremor, EEG, averaged auditory evoked response, skin conductance, heart and respiratory rate were measured.
Diazepam significantly increased the amount of fast activity (13.5–26 Hz) in the EEG but produced few peripheral effects apart from a reduction in finger tremor.
Propranolol had no central physiological effects but reduced both pulse rate and finger tremor.
The physiological effects of propranolol in chronic anxiety are different from those of diazepam and therapeutic benefit appears to be due to a direct effect on certain somatic symptoms.
Destruction of sympathetic nerve terminals with 6-hydroxydopamine (6-HO-DA) produces a small (19 per cent) but statistically significant increase in adrenal phenylethanolamine-N-methyltransferase (PNMT) activity in normal and hypophysectomized rats. This increase can be abolished by transection of the splanchnic nerves supplying the adrenal glands. The restitution of the PNMT activity by dexamethasone in hypophysectomized animals is not affected by adrenal denervation. It is concluded that the normal levels of PNMT in the adrenal medulla are maintained by adrenocortical glucocorticoids whereas an increase above the normal level can be produced by a (reflex) increase in splanchnic nerve activity. PNMT activity could not be detected in the superior cervical ganglion of controls or of animals treated with dexamethasone.
The depletion of adrenal epinephrine observed after immobilization stress in normal rats is even greater in hypophysectomized rats. The activities of adrenal tyrosine hydroxylase (TH) and phenylethanolamine-N-methyl transferase (PNMT), enzymes in the epinephrine biosynthetic pathway, are decreased following hypophysectomy. After repeated immobilization TH levels in hypophysectomized rats increase significantly but do not reach control levels. In hypophysectomized rats PNMT levels remain markedly decreased with repeated immobilization. When ACTH is administered to hypophysectomized rats before each period of immobilization there is less depletion of adrenal epinephrine and levels of TH and PNMT approach those found in sham-hypophysectomized immobilized rats. When dexamethasone is given prior to immobilization there is again less depletion of adrenal epinephrine and an increase in PNMT levels but no change in TH levels. Thyroxine does not increase epinephrine or enzyme levels in hypophysectomized immobilize...
Tyrosine hydroxylase [tyrosine monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] was highly purified from rat caudate nuclei. When the pure hydroxylase was phosphorylated by incubation with cyclic AMP-dependent protein kinase and [32P]ATP, 32P and tyrosine hydroxylase activity were detected after polyacrylamide gel electrophoresis in a single protein band. After sodium dodecyl sulfate gel electrophoresis, 32P was detected only in a probably active subunit of tyrosine hydroxylase of molecular weight 62,000. Phosphorylation of the hydroxylase increased its activity by 2-fold, and was associated with an increase in Vm without any change in Km for either substrate or cofactor. We propose that the pool of native tyrosine hydroxylase is composed of a mixture of enzyme molecules in both active and probably inactive forms, that the active form is phosphorylated, and that phosphorylation produces an active form of the enzyme at the expense of an inactive one.
Somatostatin (GHIF), when administered as a 1-hr infusion (500 mug/hr) to 5 patients with Nelson's Syndrome;resulted in a sustained, progressive fall in plasma ACTH in each patient to 40% to 71% of basal values with a return toward initail levels after cessation of the infusion. The meanreduction in plasma ADTH was 48% (p less than 0.005). These finding suggest that GHIF receptors not fuctional or present in normal pituitary tissue are present in ACTH-producing pituitary tumors.
In an attempt to understand the molecular mechanism underlying the depressive effect of glucocorticoids on corticotropin production, the level of corticotropin messenger RNA activity in rat pituitaries was measured with the use of the cell-free protein-synthesizing system derived from wheat germ. The large translation product of corticotropin messenger RNA was identified and quantitated by indirect immunoprecipitation with antibody against corticotropin. The level of corticotropin messenger RNA activity was increased 3- to 6-fold by adrenalectomy. Dexamethasone administration to adrenalectomized rats resulted in a marked suppression of corticotropin messenger RNA activity. Cortisol and corticosterone also exhibited a suppressive effect but were less effective than dexamethasone. In contrast, nonglucocorticoids such as progesterone and aldosterone had no suppressive effect. These results indicate that at least part of the glucocorticoid effect on corticotropin production in the pituitary is exerted at the pretranslational level.
Studies have been made with the mouse pituitary tumor cell line AtT-20 in culture to determine whether or not the suppression of pituitary corticotropin messenger RNA activity observed upon the administration of glucocorticoids to adrenalectomized rats is due to a direct action of these steroid hormones on the pituitary. The levels of corticotropin messenger RNA activity in AtT-20 cells treated with various steroid hormones were measured with the use of the cell-free protein-synthesizing system derived from wheat germ. The addition of dexamethasone to culture medium reduced the level of corticotropin messenger RNA activity to 30-40% of that in untreated cells. Corticosterone and cortisol exhibited a suppressive effect to a lesser extent. In contrast, nonglucocorticoids such as testosterone and 17beta-estradiol were essentially ineffective. These results indicate that at least part of the glucocorticoid action is exerted directly on the pituitary to suppress corticotropin messenger RNA activity.
The initial steps in the processing of the common precursor to adrenocorticotropin (ACTH) and endorphin in mouse pituitary tumor cells (AtT-20) have been investigated. Three forms of the precursor have been resolved by sodium dodecyl sulfate (NaDodSO4)-polyacrylamide gel electrophoresis with apparent molecular weights of 29 000 (29K ACTH-endorphin), 32 000 (32K ACTH-endorphin) and 34 000 (34K ACTH-endorphin). These forms have a similar peptide backbone, but their carbohydrate content differs. In particular, a tryptic glycopeptide has been observed in 32K ACTH-endorphin which is not present in 29K ACTH-endorphin and has been identified as the tryptic peptide containing the alpha(22--39) sequence of ACTH. Similar heterogeneity in carbohydrate has been observed in some of the smaller molecular weight forms of ACTH which are resolved by NaDodSO4 gel electrophoresis. Pulse chase and continuous labeling studies using radioactive amino acids and sugars suggest that the 29K ACTH-endorphin is converted to 32K and 34K ACTH-endorphin by the addition of carbohydrate. The glycopeptide and pulse chase studies suggest that 29K ACTH-endorphin is at a branch point in the processing pathways. It can either be converted to 4.5K ACTH by proteolytic processing or to 32K ACTH-endorphin by the further addition of carbohydrate. The 32K ACTH-endorphin can then be converted to 13K ACTH, the glycosylated form of 4.5K ACTH (Eipper, B.A., & Mains,, R.E. (1977) J.Biol. Chem.252, 882), by proteolytic processing. A comparison of the distribution of the different molecular weight forms of ACTH and endorphin in mouse pituitary extracts and in the mouse pituitary tumor cells reveals that the pituitary contains all of the forms of ACTH and endorphin seen in the tumor cells, including the three forms of the ACTH-endorphin precursor. However, the molecular weight distribution of the forms in the anterior lobe is very different from that in the intermediate lobe of mouse pituitary.
Regulation of plasma membrane receptors for peptide hormones by the prevailing ligand concentration often causes altered target cell function. Receptor number is determined by hormone-induced changes in membrane conformation, irreversible ligand binding, and processing of ligand-receptor complexes during hormone action.
Plasma epinephrine (E) and norepinephrine (NE) as well as blood pressure and heart rate variations were measured in 12 male subjects before, during, and after a cold hand test (5 degrees C for 2 min), a mental arithmetic test, and a combination of both these tests. Although the cold and mental tests had comparable effects on blood pressure, the heart rate response was greater than the mental test. The mental test produced a greater increase of E than the cold test, but the effect of the cold test was greater on NE than on E. Changes in heart rate were significantly correlated with E variations but not with NE, whereas changes in blood pressure were correlated with NE. Resting NE was correlated with resting blood pressure and resting E with resting heart rate. Finally the levels of basal E were positively correlated with the increase in E during the test. Cardiovascular changes were shown to be differently modified by a mental and a cold test. Evidence was given indicating that these changes are related to differences in E and NE responses in the presence of these tests.
Fifty-six patients with essential hypertension and 29 normotensive controls were hospitalized and volume expanded with saline or volume depleted with furosemide. We measured plasma norepinephrine (NE) and dopamine-beta-hydroxylase (DBH) to evaluate their sympathetic nervous activity. NE and DBH levels and their response to volume changes were the same in normal and hypertensive subjects. Volume depletion increased plasma NE in recumbent subjects by 50% and in standing subjects by 75% but did not alter DBH. Volume expansion with 2 liters of normal saline did not generally alter plasma NE, but led to a small decrease in DBH. Hypertensives have normal plasma levels of NE and DBH and normal responses of NE and DBH to alterations in volume and posture. The human sympathetic nervous system increases NE output during volume depletion, but fails to decrease NE during volume expansion.
Forced immobilization of rats triggers activation of adrenal-medullary discharge of epinephrine (EPI) and sympathetic neuronal release of norepinephrine (NE). Plasma levels of EPI reach peak values, which are about 40-fold greater than in undisturbed rats, at about 20 min and then decline to about one-third the peak levels. Plasma levels of NE are increased about 6-fold throughout the immobilization interval. Decapitation produces an 80-fold increase in plasma levels of EPI and an 8-fold increase in NE. These striking decapitation-induced increases are potentiated about 3-fold by immobilization, presumably as a consequence of an immobilization-induced alteration in the "set" of responsivity of spinal cord mechanisms controlling sympathoadrenal medullary discharge. Even minor disturbances produce highly significant increases in plasma EPI and NE and special precautions must be observed when studies involving plasma catecholamines or their effects are performed in animals.
Catecholamines (adrenaline, noradrenaline and dopamine) have been measured in specific areas of the rat brain stem after acute immobilization stress. Adrenaline levels were significantly decreased after 240 min of immobilization in all areas studied: A1 area, nucleus commissuralis (NCO), A2 area, anterior part of the nucleus tractus solitarii (NTS), and the locus coeruleus. Noradrenaline concentrations in stressed rats were significantly reduced only in the NTS area. In contrast, during stress there were no significant changes in dopamine concentrations with respect to control values in any of the areas studied. These results implicate the participation of central adrenaline neurons, localized in specific brain stem areas, and noradrenaline neurons innervating the rostral part of the nucleus tractus solitarii, in the mechanism of central response to acute stress.
Both plasma norepinephrine and epinephrine increase during exercise. Briefly, norepinephrine is correlated to hemodynamic parameters and oxygen requirement while plasma epinephrine is dependent on both sympathetic nervous activity and blood glucose concentration.
Modification of the original single isotope radioenzymatic assay of Passon and Peuler (1) permits the direct and simultaneous analysis of norepinephrine, epinephrine and dopamine in plasma samples of 50 μl or less. Plasma or cerebrospinal fluid without prior extraction of catecholamines or deproteinization is added directly into a mixture of 100 μl. This catechol-O-methyl-transferase-catalyzed assay is sensitive to 1 pg (20 pg/ml of plasma) for norepinephrine and epinephrine and 6 pg (120 pg/ml) for dopamine. A rapid thin layer chromatographic separation of the three 3H-methylcatecholamines contributes to the excellent specificity of the differential assay of the three catecholamines. The differential analysis of 15–20 plasma samples can be completed easily within one day. A total assay which omits the chromatographic step and, thus, measures norepinephrine plus epinephrine at the same sensitivity can be completed in 20 samples in one-half a working day.
In order to determine whether the sympathetic nervous system participates in the neuroendocrine response to surgical stress in man, plasma levels of norepinephrine (NE) and epinephrine (E) were measured by enzymatic assay in eight patients undergoing elective abdominal operations. Basal NE levels (pre-anesthesia) were comparable to those of 11 normal controls: 180 ± 20 pg/ml, X ± SEM (patients), vs. 180 ± 20 (controls), but basal E levels were higher: 70 ± 10 (patients) vs. 20 ± 5 (controls), P < .001. Halothane anesthesia caused no changes of plasma NE (Δ NE = +50 ± 40 pg/ml, p = NS), but suppressed plasma E (Δ E = -50 ± 10 pg/ml, P < .01). During the operation plasma catecholamines rose above anesthesia levels in all patients: Δ NE = +380 ± 60, Δ E = +250 ± 100, both P < .01. Plasma catecholamines remained elevated through 2 h after surgery: Δ NE (vs. pre-anesthesia baseline) = +290 ± 60, P < .01, Δ E = +200 ± 60, P < .05. Throughout the procedure Δ NE correlated with Δ E (r = .75, P < .001). These findings indicate that adrenergic activation does occur during surgical stress in man. This activation is not due to anesthesia, which appears to suppress E release. During these studies Δ mean arterial pressure correlated positively both with Δ NE (r = .68, P < .001) and with Δ E (r = .73, P < .001), indicating that the increases of adrenergic activity were associated with increases of mean arterial pressure and were not a response to hypotension or hypovolemia. Changes of plasma catecholamine levels were unrelated to either hypoxia or hypothermia. Thus, the increases of NE and E during surgical stress may reflect an adrenergic response to afferent pain stimuli which are not blocked by anesthesia.
Levels of norepinephrine (NE) in human plasma have been determined by a radioenzymatic technique sufficiently sensitive to measure 0.014 ng NE per ml plasma. Several procedures which raise plasma NE levels have been compared and a standard procedure developed to evaluate sympathetic neuronal function based on the increments in plasma NE produced by postural change and a standard amount of exertion. The mean basal level of NE in plasma of 74 resting, supine, normal subjects ranging in age from 10 to 70 (mean 32.7 years) was 0.292 ± 0.016 (± SEM) ng/ml and ranged from 0.112 to 0.738 ng/ml. There was a significant correlation between age and basal levels of NE (L.R. = 0.33, p < 0.01). In 44 subjects who stood for 5 minutes after the basal sample of blood was obtained, the mean plasma level of NE increased to 0.538 ± 0.044 ng/ml and further increased to 0.778 ± 0.080 ng/ml after a subsequent isometric hand grip for 5 minutes.
The authors report on the effects of propranolol, a beta-adrenergic blocking agent, on 10 patients with pathological panic states. Propranolol was effective in treating acute pathological panic, but modest doses of the drug administered for brief periods of time did not alleviate chronic panic attacks associated with agoraphobia. The drug suppressed panic associated with depressive syndromes but did not affect the depression and had no clear effect on anticipatory anxiety. The authors suggest that further study of these findings may clarify other clinical problems.
A radiometric-enzymatic assay for measuring simultaneously femtomole quantities of adrenaline, noradrenaline and dopamine has been developed. The three catecholamines are first converted to their O-methylated analogues by catechol-O-methyltransferase in the presence of S-adenosyl-methionine-3H and thereafter extracted following addition of sodium tetraphenylborate. This extraction, together with an improved quick chromatographic separation and the oxidation of the adrenaline and noradrenaline derivatives to vanillin, yields an extremely high sensitivity and specificity of the method.The present assay allows the determination of adrenaline, noradrenaline and dopamine in tissue samples with a protein content of 100 μg or less and in plasma volumes of 20 – 100 μl. The amine content of 40 – 50 samples can be determined in two days by one person.Due to the high sensitivity achieved, this method promises to be a valid alternative to the gas chromatography-mass spectrometry technique.
Eight men were studied during graded (47, 77, and 100% of maximal oxygen uptake) and prolonged (76%) exhaustive treadmill running. During graded exercise the glucagon concentration increased 35% from 81 plus or minus 7 pg/ml (mean and SE) at rest to 109 plus or minus 17 after the heaviest load. During prolonged exercise glucagon increased progressively to three times (226 plus or minus 40) the resting value. Norepinephrine increased from 0.40 plus or minus 0.06 ng/ml to 2.22 plus or minus 0.39, epinephrine from 0.07 plus or minus 0.01 to 0.42 plus or minus 0.13 during graded, and to 1.51 plus or minus 0.08 and 0.33 plus or minus 0.04, respectively, during prolonged exercise. Insulin concentrations were depressed during work except for the heaviest load. Fatty acids rose throughout prolonged exercise, whereas blood glucose significantly diminished 30 min afterward. Glucagon concentrations correlated significantly with norepinephrine and epinephrine concentrations during prolonged and with epinephrine during graded exercise. Although increments in catecholamines were similar, the glucagon secretion was larger during prolonged than during graded exercise. While increments in catecholamines might explain increased glucagon secretion during graded exercise, they cannot account completely for the rise of glucagon during prolonged exercise.
The activity of phenylethanolamine-N-methyl transferase, an enzyme that synthesizes adrenaline from noradrenaline in the adrenal medulla, is markedly depressed following hypophysectomy. Enzyme activity is restored to normal after administration of ACTH or the potent glucocorticoid, dexamethasone. Thus the biosynthesis of adrenaline in the adrenal medulla appears to be regulated by the pituitary-adrenocortical system.
AFTER the destruction of sympathetic nerve endings by 6-hydroxydopamine1,2, there is a compensatory increase in the catecholamine synthesis and tyrosine hydroxylase activity in the adrenal gland3. We have examined the actions of reserpine and phenoxybenzamine on adrenal tyrosine hydroxylase activity. These drugs, like 6-hydroxydopamine2, interfere with postganglionic sympathetic transmission, but by different mechanisms4-6. We also studied the alterations of this enzyme in an embryologically related tissue, the superior cervical sympathetic ganglion. Reserpine and phenoxybenzamine increased the activity of adrenal tyrosine hydroxylase, and reserpine also increased the activity of tyrosine hydroxylase in the superior cervical ganglion. This increase in enzyme activity was prevented by interruption of nerve impulses by decentralization.
To determine whether vasopressin affects the sensitivity of the anterior pituitary to corticotropin-releasing factor, vasopressin was administered intravenously in doses subthreshold with respect to ACTH release to rats pretreated with dexamethasone (dex), Nembutal (Nem), and, sometimes, also morphine (morph). Crude ovine CRF was given intravenously immediately following the vasopressin. The adrenocortical response to CRF was increased at least 100% by the prior administration of subthreshold doses of vasopressin. When 1/20 of the intravenous dose of vasopressin was placed into both lobes of the anterior pituitary it again failed to release ACTH itself, but increased 2.5 times the response to CRF given intravenously. This potentiation of CRF-induced ACTH release by vasopressin at the adenohypophysis was not observed if the vasopressin was administered into one lobe only of the anterior pituitary. In rats pretreated with dex +Nem the potentiation was the same as in those pretreated with dex + Nem+morph. Oxytocin did not potentiate the action of CRF, and vasopressin did not potentiate the adrenal gland response to ACTH. In experiments with a reversed sequence of injection, the administration of subthreshold doses of CRF prior to suprathreshold doses of vasopressin failed to reveal any potentiation of vasopressininduced activation of the adrenocortical system by the CRF. In rats congenitally lacking vasopressin (Brattleboro strain) adrenal response to ACTH was normal, whereas the adrenal cortical response to all submaximal stresses tested was impaired. In dehydrated normal rats, the response to CRF was enhanced. A schema reconciling all these findings is presented. (Endocrinology 88: 3, 1971)
To determine whether vasopressin affects the sensitivity of the anterior pituitary to corticotropin-releasing factor, vasopressin was administered intravenously in doses subthreshold with respect to ACTH release to rats pretreated with dexamethasone (dex), Nembutal (Nem), and, sometimes, also morphine (morph). Crude ovine CRF was given intravenously immediately following the vasopressin. The adrenocortical response to CRF was increased at least 100% by the prior administration of subthreshold doses of vasopressin. When 1/20 of the intravenous dose of vasopressin was placed into both lobes of the anterior pituitary it again failed to release ACTH itself, but increased 2.5 times the response to CRF given intravenously. This potentiation of CRF-induced ACTH release by vasopressin at the adenohypophysis was not observed if the vasopressin was administered into one lobe only of the anterior pituitary. In rats pretreated with dex +Nem the potentiation was the same as in those pretreated with dex + Nem+morph. Oxytocin did not potentiate the action of CRF, and vasopressin did not potentiate the adrenal gland response to ACTH. In experiments with a reversed sequence of injection, the administration of subthreshold doses of CRF prior to suprathreshold doses of vasopressin failed to reveal any potentiation of vasopressininduced activation of the adrenocortical system by the CRF. In rats congenitally lacking vasopressin (Brattleboro strain) adrenal response to ACTH was normal, whereas the adrenal cortical response to all submaximal stresses tested was impaired. In dehydrated normal rats, the response to CRF was enhanced. A schema reconciling all these findings is presented. (Endocrinology 88: 3, 1971)
An assay for plasma norepinephrine and epinephrine levels has been developed by the modification of published procedures. The plasma norepinephrine and epinephrine assay, when compared to currently available methods, provides a substantial decrease in the assay time while providing a 10-fold increase in sensitivity which allows the analysis to be performed on 0.75 ml or less of plasma. Norepinephrine and epinephrine are converted to their O-methylated analogs in the presence of catechol-O-methyl transferase and S-adenosylmethionine-methyl-3H. Following purification of the labelled normetanephrine and metanephrine by solvent extraction and thinlayer chormatography, the amines are oxidized to vanillin, purified by solvent extraction and counted. The specificity, linearity and precision of the assay are discussed.
As an initial step in studying the mechanism of feedback inhibition of adrenocorticotropic hormone (ACTH) by glucocorticoids, the effect of these steroid hormones on ACTH production was studied in AtT 20, a cloned mouse pituitary tumor cell line grown in tissue culture. ACTH levels in cells and medium were measured by bioassay in the hypophysectomized rat and found to be depressed after treatment with dexamethasone, triamcinolone, corticosterone and cortisol, but not significantly affected by nonglucocorticoid hormones. The reduction of both intracellular and extracellular ACTH suggested a primary effect of glucocorticoids on ACTH synthesis. The steroid effects were produced without any detectable change in cell number or total protein levels, suggesting a specific effect on ACTH. This single cell system promises to be a valuable tool for further studies on factors regulating the synthesis and secretion of ACTH.
The increase in tyrosine hydroxylase activity in the rat superior cervical ganglion produced by reserpine is abolished by decentralization or administration of the nicotinic blockers chlorisondamine and pempidine. In contrast, the rise in adrenal tyrosine hydroxylase activity is neither inhibited by nicotinic nor muscarinic receptor blockers, although it is abolished by splanchnic transection. Since chlorisondamine and pempidine diminish the magnitude of adrenal catecholamine depletion produced by reserpine to the same extent as denervation, it is unlikely that incomplete blockade of the nicotinic receptors is responsible for the inability to block the increase in adrenal enzyme activity. It is possible that in the adrenal medulla either another cholinergic receptor or another neurotransmitter is involved in mediating the trans-synaptic increase in tyrosine hydroxylase.Pempidine, chlorisondamine and atropine all produce an increase in adrenal tyrosine hydroxylase when used alone. This can be prevented by prior splanchnic transection.