Plasma Glucocorticoid Concentrations Research Articles

The relationship between hypoxia exposure and circulating cortisol levels in social and solitary African mole-rats: An initial report

Hypoxemia from exposure to intermittent and/or acute environmental hypoxia (lower oxygen concentration) is a severe stressor for many animal species. The response to hypoxia of the hypothalamic–pituitary-adrenal axis (HPA-axis), which culminates in the release of glucocorticoids, has been well-studied in hypoxia-intolerant surface-dwelling mammals. Several group-living (social) subterranean species, including most African mole-rats, are hypoxia-tolerant, likely due to regular exposure to intermittent hypoxia in their underground burrows. Conversely, solitary mole-rat species, lack many adaptive mechanisms, making them less hypoxia-tolerant than the social genera. To date, the release of glucocorticoids in response to hypoxia has not been measured in hypoxia-tolerant mammalian species. Consequently, this study exposed three social African mole-rat species and two solitary mole-rat species to normoxia, or acute hypoxia and then measured their respective plasma glucocorticoid (cortisol) concentrations. Social mole-rats had lower plasma cortisol concentrations under normoxia than the solitary genera. Furthermore, individuals of all three of the social mole-rat species exhibited significantly increased plasma cortisol concentrations after hypoxia, similar to those of hypoxia-intolerant surface-dwelling species. By contrast, individuals of the two solitary species had a reduced plasma cortisol response to acute hypoxia, possibly due to increased plasma cortisol under normoxia. If placed in perspective with other closely related surface-dwelling species, the regular exposure of the social African mole-rats to hypoxia may have reduced the basal levels of the components for the adaptive mechanisms associated with hypoxia exposure, including circulating cortisol levels. Similarly, the influence of body mass on plasma cortisol levels cannot be ignored. This study demonstrates that both hypoxia-tolerant rodents and hypoxia-intolerant terrestrial laboratory-bred rodents may possess similar HPA-axis responses from exposure to hypoxia. Further research is required to confirm the results from this pilot study and to further confirm how the cortisol concentrations may influence responses to hypoxia in African mole-rats.

Transcriptional and cell type profiles of cortical brain regions showing ultradian cortisol rhythm dependent responses to emotional face stimulation

The characteristic endogenous circadian rhythm of plasma glucocorticoid concentrations is made up from an underlying ultradian pulsatile secretory pattern. Recent evidence has indicated that this ultradian cortisol pulsatility is crucial for normal emotional response in man. In this study, we investigate the anatomical transcriptional and cell type signature of brain regions sensitive to a loss of ultradian rhythmicity in the context of emotional processing. We combine human cell type and transcriptomic atlas data of high spatial resolution with functional magnetic resonance imaging (fMRI) data. We show that the loss of cortisol ultradian rhythm alters emotional processing response in cortical brain areas that are characterized by transcriptional and cellular profiles of GABAergic function. We find that two previously identified key components of rapid non-genomic GC signaling – the ANXA1 gene and retrograde endocannabinoid signaling – show most significant differential expression (q = 3.99e−10) and enrichment (fold enrichment = 5.56, q = 9.09e−4). Our results further indicate that specific cell types, including a specific NPY-expressing GABAergic neuronal cell type, and specific G protein signaling cascades underly the cerebral effects of a loss of ultradian cortisol rhythm. Our results provide a biological mechanistic underpinning of our fMRI findings, indicating specific cell types and cascades as a target for manipulation in future experimental studies.

GLUCOCORTICOID EXCESS INDUCES NON-DIPPING BLOOD PRESSURE AND RENAL VASCULAR DYSFUNCTION

Abstract Objective: Blood pressure (BP) abnormalities such as loss/attenuation of nocturnal BP dip (non-dipping) increase cardiovascular risk. The mechanisms underlying non-dipping are not clear, but renal and vascular dysfunction has been implicated. People with abnormal glucocorticoid (GC) homeostasis, such as in Cushing's syndrome, often display non-dipping BP therefore, here we investigated the contribution of GCs to BP rhythmicity. Design and method: The effect of GC excess, driven by ACTH infusion, on BP and plasma GC rhythmicity was examined in adult male C57BL/6J mice. Radiotelemetry was used to measure BP longitudinally before and after ACTH infusion (2.5 mg/day for 14days via minipump). Diurnal plasma GCs was measured by ELISA. Diurnal renal vascular function was investigated ex vivo by wire myography in isolated renal arteries from separate cohorts of mice either control or ACTH-treated collected between 7–8AM (day) or 7–8PM (night). Vascular reactivity to vasoconstrictor phenylephrine (PHE), endothelium-dependent acetylcholine (ACh) and endothelium-independent sodium nitroprusside (SNP) vasodilators was assessed. Data are mean ± SD. Results: After 5days of baseline measurements, 24-hour systolic BP (SBP) was 123.8 ± 4.2 mmHg and 24-hour diastolic BP (DBP) was 96.2 ± 5.6 mmHg. The day:night SBP and DBP variation was 12.8 ± 4.5 mmHg and 12.3 ± 4.8 mmHg, respectively. ACTH-excess increased 24-hour SBP to 133.8 ± 1.7 mmHg and 24-hour DBP to 101.4 ± 2.1 mmHg. The day:night SBP and DBP variation was reduced to 0.6 ± 7.2 mmHg (p = 0.0166) and 2.4 ± 9.6 mmHg (p = 0.0235), respectively. Day:night activity count during BP measurements was similar before and after ACTH infusion. Diurnal plasma GCs was increased following ACTH infusion, compared with baseline (p < 0.0001). Furthermore, ACTH-excess flipped the diurnal rhythm of GC, so the day plasma GC concentration is higher than the night. Day control renal arteries showed a trend for an increase in sensitivity to PHE (p = 0.0578) and SNP (p = 0.0795), with no changes in ACh (p = 0.1299), compared with night control renal arteries. ACTH-excess caused no differences in day and night responses to PHE (p = 0.5526), ACh (p = 0.1169), and SNP (p = 0.9466). ACTH-excess caused renal vascular dysfunction, compared with controls, causing a significant reduction in sensitivity to PHE (p = 0.0005), ACh (p = 0.0128) and SNP (p = 0.0002). Conclusions: These data show that chronic GC induces non-dipping BP and renal vascular dysfunction.

Biomarkers for classification and class prediction of stress in a murine model of chronic subordination stress.

Selye defined stress as the nonspecific response of the body to any demand and thus an inherent element of all diseases. He reported that rats show adrenal hypertrophy, thymicolymphatic atrophy, and gastrointestinal ulceration, referred to as the stress triad, upon repeated exposure to nocuous agents. However, Selye’s stress triad as well as its extended version including reduced body weight gain, increased plasma glucocorticoid (GC) concentrations, and GC resistance of target cells do not represent reliable discriminatory biomarkers for chronic stress. To address this, we collected multivariate biological data from male mice exposed either to the preclinically validated chronic subordinate colony housing (CSC) paradigm or to single-housed control (SHC) condition. We then used principal component analysis (PCA), top scoring pairs (tsp) and support vector machines (SVM) analyses to identify markers that discriminate between chronically stressed and non-stressed mice. PCA segregated stressed and non-stressed mice, with high loading for some of Selye’s stress triad parameters. The tsp analysis, a simple and highly interpretable statistical approach, identified left adrenal weight and relative thymus weight as the pair with the highest discrimination score and prediction accuracy validated by a blinded dataset (92% p-value < 0.0001; SVM model = 83% accuracy and p-value < 0.0001). This finding clearly shows that simultaneous consideration of these two parameters can be used as a reliable biomarker of chronic stress status. Furthermore, our analysis highlights that the tsp approach is a very powerful method whose application extends beyond what has previously been reported.

The defensive behavioral patterns of captive white-lipped and collared peccary (Mammalia, Tayassuidae): an approach for conservation of the species

Defensive behavioral patterns in response to human-induced rapid environmental change can affect animals’ fitness and may play a role in species conservation status. To test this hypothesis, we compared the risk assessment and defensive behavioral responses of captive white-lipped peccary (WLP; Tayassu pecari) and collared peccary (CP; Pecari tajacu), which retain different conservation status; WLP are considered vulnerable and CP of least concern. We used an adapted paradigm of the mouse defense test battery (MDTB) comprising four consecutive tests. Two of these tests simulated a novel environment, while the other two stimulated the expression of defensive behavioral patterns. Besides differences in risk assessment and defensive threat/attack behavioral patterns between species, we compared flight initiation distance, flight speed, and plasma glucocorticoid concentrations. When facing a novel environment and risk challenges from humans’ predator-like cues, the white-lipped peccary showed more exploratory and defensive threat/attack behavioral patterns, shorter flight initiation distances, and lower flight speeds, whereas the collared peccaries showed more cautious and retreat patterns, longer flight initiation distances, and higher flight speeds. There were also correlations between physiological and behavioral parameters. We confirmed our hypothesis that the collared peccary’s cautiousness may help to prevent a decrease in its population, while the white-lipped peccary’s exploratory and confrontational behavioral patterns in overhunted areas, together with other simultaneous factors as forest fragmentation, might contribute to placing this species in the vulnerable category.

Dehydration enhances multiple physiological defense mechanisms in a desert lizard, Heloderma suspectum.

The physiological challenges associated with dehydration can induce an increase in plasma glucocorticoid concentrations, a response thought to provide the mechanism for dehydration suppressing immune function. However, a comprehensive examination of the inter-relationship of dehydration, stress and immune function has not been conducted within a single species. We previously demonstrated that Gila monsters (Heloderma suspectum), which inhabit a xeric environment with a predictable seasonal drought, have enhanced measures of innate immunity when dehydrated. These results suggest that, in this species, dehydration may not induce a glucocorticoid response, but, instead, enhances physiological defense mechanisms. To explore this possibility, we examined multiple measures of innate immunity as well as initial and reactive plasma concentrations of glucocorticoids in captive and free-ranging Gila monsters at various hydration states. Our results show that, in this species, dehydration alone does not cause a substantial increase in plasma glucocorticoids, and we provide broader evidence that dehydration enhances defensive mechanisms including stress reactivity and various measures of innate immune function. These findings suggest that physiological responses to dehydration may depend heavily on an organism's ecology. More research on the effects of dehydration on the glucocorticoid response and immunity will help clarify the interactive roles they play in response to hydration challenges and whether adaptations to water-limited environments influence these interactions.

Beeswax corticosterone implants produce long-term elevation of plasma corticosterone and influence condition

Glucocorticoids can play a critical role in modulating life-history trade-offs. However, studying the effects of glucocorticoids on life-history often requires experimentally elevating plasma glucocorticoid concentrations for several weeks within normal physiological limits and without repeated handling of the animal. Recently, implants made of beeswax and testosterone (T) were shown to have release dynamics superior to some currently available T implants, and these beeswax implants dissolved, eliminating the need to recapture the animal. We evaluated the utility of beeswax implants containing four different dosages of corticosterone (CORT; the primary glucocorticoid in birds) and their effect on several condition indices in a captive colony of zebra finches (Taeniopygia guttata). The three implants with the greatest CORT doses (0.05, 0.1, and 0.5mg) produced spikes in plasma CORT concentrations 20h after treatment, but were within the limits that zebra finches may normally experience. The 0.5mg CORT implant elevated plasma CORT between typical baseline and restraint stress levels reported in other studies of zebra finches for the entire 35day experiment. Birds in the 0.5mg implant group were heavier, had greater furcular fat scores, and had lower hematocrit than birds in the control and other CORT implant groups. Beeswax CORT implants are a low cost method of elevating plasma CORT for a prolonged time. Furthermore, because there is no need to remove these implants at the end of a study, this method may be amenable to studies of free-ranging animals.

Mineralocorticoid receptor activation and mineralocorticoid receptor antagonist treatment in cardiac and renal diseases.

Cardiac and renal diseases remain major challenges for healthcare systems in developed countries and commonly coexist, with a disorder in the heart or kidney often leading to secondary dysfunction or injury in the other organ. Indeed, the term cardiorenal syndrome has been introduced to describe the broad spectrum of disease involving both the heart and kidneys.1 Aldosterone is a steroid hormone with mineralocorticoid activity, produced primarily in the glomerular zone of the adrenal cortex.2 Aldosterone fulfills its major physiological function of maintaining sodium and potassium balance and blood pressure control by binding to the mineralocorticoid receptor (MR) in the connecting tubule and cortical collecting duct in the kidneys, thereby increasing sodium reabsorption and potassium secretion. There is a growing body of evidence for a broader role of aldosterone and MR activation in the pathophysiology of cardiovascular and renal disease.3,4 This article focuses on our knowledge and understanding of the direct roles of aldosterone and MR activation in the heart and kidneys, including common pathophysiological mechanisms in both organs and implications for clinical use of MR antagonists (MRAs) in the treatment of cardiac and renal diseases. MR expression has been demonstrated in vivo in vascular endothelial cells and vascular smooth muscle cells of interlobar arteries in mouse kidneys and ex vivo in cultured podocytes, mesangial cells, and renal fibroblasts.3 The MR is also expressed in multiple cell types in the heart, including cardiomyocytes, coronary endothelial and vascular smooth muscle cells, fibroblasts, and inflammatory cells, such as macrophages.5 Aldosterone and the glucocorticoid cortisol bind to the MR with similar affinities. Plasma concentrations of glucocorticoids are 100- to 1000-fold higher than those of aldosterone. Overstimulation of the MR is prevented by the coexpression of 11β-hydroxysteroid dehydrogenase type 2 (11-BHSD2). This enzyme converts cortisol into cortisone, which …

Effects of age and chronic alcohol self‐administration on plasma mineralocorticoid and glucocorticoid concentrations in male rhesus monkeys

To investigate the mechanisms mediating blunted hypothalamic‐pituitary‐adrenal (HPA) axis in alcoholics, we measured plasma mineralocorticoids (deoxycorticosterone, DOC; aldosterone, ALD) and glucocorticoids (cortisol) in male rhesus monkeys during controlled induction of alcohol drinking then 12 months of daily “open access” to alcohol and water for 22 h/d. Heavy alcohol drinking was defined &gt;; 3.0 g/kg/d alcohol (~12 drinks). Morning hormones were measured for ~20 months at ~6–8‐week intervals in four cohorts of differing ages, basal testosterone and alcohol intake: adolescents, 3/8 heavy drinkers; young adults, two cohorts; older adults, 0/11 heavy drinkers. Four adolescent monkeys were isocaloric controls. Perhaps related to environmental history, one of the young adult cohorts had greater testosterone at baseline (5/8 heavy drinkers) compared to the other (0/8 heavy drinkers). ALD and DOC were constant except amongst adolescent monkeys, for whom DOC decreased during open access. Cortisol decreased during open access compared to induction, significantly for the heaviest drinkers. Glucocorticoids were more sensitive than mineralocorticoids to chronic alcohol self‐administration. Early age of onset may increase mineralocorticoid regulation by alcohol that could contribute to later heavy drinking, e.g., via neuroactive steroid metabolites like allotetrahydrodeoxycorticosterone.

Influence of body condition on plasma prednisolone and prednisone concentrations in clinically healthy cats after single oral dose administration

Influence of body condition (over-conditioned vs. normal-conditioned) on plasma glucocorticoid concentrations after single dose oral prednisolone or prednisone in 11 cats (5 normal-conditioned and 6-over-conditioned) was investigated using a two-drug crossover trial (3-week washout interval). Body condition was determined using criterion-referenced bioelectrical impedance together with plasma drug concentrations (prednisolone [active drug] and prednisone [pro-drug]) measured by HPLC. Although interconversion of each drug to the other was confirmed, a single 2mg/kg body weight oral dose of prednisolone produced significantly higher plasma prednisolone concentration (∼4-fold higher AUC) compared to prednisone. Significantly higher plasma drug concentrations in over-conditioned cats (∼2-fold) compared to normal-conditioned cats might explain their perceived increased risk for glucocorticoid associated side effects (hepatic lipidosis, diabetes mellitus). Findings suggest low comparative bioavailability of oral prednisone compared to prednisolone in cats and consideration of lean body mass or ideal body weight for dosing practices.

Partial protection from organophosphate-induced cholinesterase inhibition by metyrapone treatment

Organophosphates are cholinesterase (ChE) inhibitors with worldwide use as insecticides. Stress response, evidenced by a dramatic and relatively long-lasting (several hours) rise in the plasma glucocorticoid concentration is an integral element of the organophosphate (OP) poisoning symptomatology. In rodents, corticosterone (CORT) is the main glucocorticoid. There are several reports suggesting a relationship between the stressor-induced rise in CORT concentration (the CORT response) and the activity of the cerebral and peripheral ChE. Thus, it seems reasonable to presume that, in OP intoxication, the rise in plasma CORT concentration may somehow affect the magnitude of the OP-induced ChE inhibition. Metyrapone (MET) [2-methyl-1,2-di(pyridin-3-yl)propan-1-one] blocks CORT synthesis by inhibiting steroid 11β-hydroxylase, thereby preventing the CORT response. Chlorfenvinphos (CVP) [2-chloro-1-(2,4-dichlorophenyl) ethenyl diethyl phosphate] is an organophosphate insecticide still in use in some countries. The purpose of the present work was to compare the CVP-induced effects - the rise of the plasma CORT concentration and the reduction in ChE activity - in MET-treated and MET-untreated rats. Chlorfenvinphos was administered once at 0.0, 0.5, 1.0 and 3.0 mg/kg i.p. Metyrapone, at 100 mg/kg i.p., was administered five times, at 24-h intervals. The first MET dose was given two hours before CVP. The following was observed in the MET-treated rats: i) no rise in plasma CORT concentration after the CVP administration, ii) a reduced inhibition and a faster restitution of blood and brain ChE activities. The results suggest that MET treatment may confer significant protection against at least some effects of OP poisoning. The likely mechanism of the protective MET action has been discussed.

Sex-differences and seasonal changes in plasma glucocorticoid concentrations in European beaver (Castor fiber)

Sex-differences and seasonal changes in plasma glucocorticoid concentrations in European beaver (Castor fiber)

Effects of cortisol and dexamethasone on insulin signalling pathways in skeletal muscle of the ovine fetus during late gestation.

Before birth, glucocorticoids retard growth, although the extent to which this is mediated by changes in insulin signalling pathways in the skeletal muscle of the fetus is unknown. The current study determined the effects of endogenous and synthetic glucocorticoid exposure on insulin signalling proteins in skeletal muscle of fetal sheep during late gestation. Experimental manipulation of fetal plasma glucocorticoid concentration was achieved by fetal cortisol infusion and maternal dexamethasone treatment. Cortisol infusion significantly increased muscle protein levels of Akt2 and phosphorylated Akt at Ser473, and decreased protein levels of phosphorylated forms of mTOR at Ser2448 and S6K at Thr389. Muscle GLUT4 protein expression was significantly higher in fetuses whose mothers were treated with dexamethasone compared to those treated with saline. There were no significant effects of glucocorticoid exposure on muscle protein abundance of IR-β, IGF-1R, PKCζ, Akt1, calpastatin or muscle glycogen content. The present study demonstrated that components of the insulin signalling pathway in skeletal muscle of the ovine fetus are influenced differentially by naturally occurring and synthetic glucocorticoids. These findings may provide a mechanism by which elevated concentrations of endogenous glucocorticoids retard fetal growth.

Effect of stress on hippocampal nociceptin expression in the rat

Nociceptin/orphanin FQ (N/OFQ) peptide and its receptor are not only ubiquitously expressed in mammalian brain and spinal cord but are also abundant in limbic structures, particularly in the hippocampus. The widespread distribution of N/OFQ reflects the broad spectrum of its biological actions such as nociception, food intake, spontaneous locomotor activity, and learning and memory processes. Since the hippocampus is involved in the control of adrenocortical activity, its role in stress-related phenomena is well characterized. In male Wistar rats, we first examined the effects of acute restraint stress (120 min) on the brain immunohistochemical localization of N/OFQ. The analysis carried out on sections obtained at the onset of stress revealed enhanced expression of N/OFQ in CA1, CA3, and the dentate gyrus as well as increased plasma corticosterone concentrations. Next, we examined whether endogenous glucocorticoid hormone plays a role in the modulation of hippocampal N/OFQ expression in response to stress. To this end, rats were injected with corticosterone (1 mg/kg) or subjected to restraint stress 1 week after adrenalectomy. Two hours after corticosterone administration, plasma glucocorticoid concentrations were comparable to those observed after restraint stress, while N/OFQ expression had significantly increased in all the hippocampal subfields examined. By contrast, in adrenalectomized rats, stress did not modify protein expression. These results confirm that stress can affect N/OFQ expression and that glucocorticoids may constitute hormonal mediators of this complex interplay.

Effects of antisense-mediated inhibition of 11β-hydroxysteroid dehydrogenase type 1 on hepatic lipid metabolism

11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) converts inactive 11-keto derivatives to active glucocorticoids within tissues and may play a role in the metabolic syndrome (MS). We used an antisense oligonucleotide (ASO) to knock down 11β-HSD1 in livers of C57BL/6J mice consuming a Western-type diet (WTD). 11β-HSD1 ASO-treated mice consumed less food, so we compared them to ad libitum-fed mice and to food-matched mice receiving control ASO. Knockdown of 11β-HSD1 directly protected mice from WTD-induced steatosis and dyslipidemia by reducing synthesis and secretion of triglyceride (TG) and increasing hepatic fatty acid oxidation. These changes in hepatic and plasma lipids were not associated with reductions in genes involved in de novo lipogenesis. However, protein levels of both sterol regulatory element-binding protein (SREBP) 1 and fatty acid synthase were significantly reduced in mice treated with 11β-HSD1 ASO. There was no change in hepatic secretion of apolipoprotein (apo)B, indicating assembly and secretion of smaller apoB-containing lipoproteins by the liver in the 11β-HSD1-treated mice. Our results indicate that inhibition of 11β-HSD1 by ASO treatment of WTD-fed mice resulted in improved plasma and hepatic lipid levels, reduced lipogenesis by posttranslational regulation, and secretion of similar numbers of apoB-containing lipoproteins containing less TG per particle.

Glucocorticoid-mediated nycthemeral and photoperiodic regulation of tph2 expression

In the Syrian hamster dorsal and median raphé nuclei, the tryptophan hydroxylase 2 gene (tph2), which codes the rate-limiting enzyme of serotonin synthesis, displays daily variations in its expression in animals entrained to a long but not to a short photoperiod. The present study aimed to assess the role of glucocorticoids in the nycthemeral and photoperiodic regulation of daily tph2 expression. In hamsters held in long photoperiod from birth, after adrenalectomy and glucocorticoid implants the suppression of glucocorticoid rhythms induced an abolition of the daily variations in tph2-mRNA concentrations, a decrease in the amplitude of body temperature rhythms and an increase in testosterone levels. All these effects were reversed after experimental restoration of a clear daily rhythm in the plasma glucocorticoid concentrations. We conclude that the photoperiod-dependent rhythm of glucocorticoids is the main regulator of tph2 daily expression.

Vascular hyporesponsiveness to vasopressors in septic shock: from bench to bedside

To delineate some of the characteristics of septic vascular hypotension, to assess the most commonly cited and reported underlying mechanisms of vascular hyporesponsiveness to vasoconstrictors in sepsis, and to briefly outline current therapeutic strategies and possible future approaches. Source data were obtained from a PubMed search of the medical literature with the following MeSH terms: Muscle, smooth, vascular/physiopathology; hypotension/etiology; shock/physiopathology; vasodilation/physiology; shock/therapy; vasoconstrictor agents. Nitric oxide (NO) and peroxynitrite are crucial components implicated in vasoplegia and vascular hyporeactivity. Vascular ATP-sensitive and calcium-activated potassium channels are activated during shock and participate in hypotension. In addition, shock state is characterized by inappropriately low plasma glucocorticoid and vasopressin concentrations, a dysfunction and desensitization of alpha-receptors, and an inactivation of catecholamines by oxidation. Numerous other mechanisms have been individualized in animal models, the great majority of which involve NO: MEK1/2-ERK1/2 pathway, H(2)S, hyperglycemia, and cytoskeleton dysregulation associated with decreased actin expression. Many therapeutic approaches have proven their efficiency in animal models, especially therapies directed against one particular compound, but have otherwise failed when used in human shock. Nevertheless, high doses of catecholamines, vasopressin and terlipressin, hydrocortisone, activated protein C, and non-specific shock treatment have demonstrated a partial efficiency in reversing sepsis-induced hypotension.

Mellowing with age: older parents are less responsive to a stressor in a long‐lived seabird

Summary 1. Reproductive success often increases with age; however the mechanisms underlying this commonly observed pattern are poorly understood. One mechanism that may be important is a set of physiological responses (the stress response) that allows organisms to evade and cope with stressors, but often inhibits reproduction. 2. If older parents respond less strongly to stressors than younger parents, this age‐related difference in the stress response may contribute to the higher reproductive success that often characterizes older parents. 3. Typically the stress response is measured as an increase in plasma glucocorticoid (CORT) concentration, and we have previously reported that stress‐induced CORT levels decline with age in the common tern (Sterna hirundo). Another hormone, prolactin (PRL), has been reported to decrease in response to stressors in breeding birds and is often positively associated with parental behaviour. We predicted that like the CORT stress response, the PRL stress response would also be suppressed with age. 4. To test this prediction, we captured known‐age, incubating common terns ranging in age from 3 to 29 years and measured stress‐induced changes in PRL and CORT levels within the same individuals. 5. We found that PRL levels decreased less rapidly in response to capture and restraint stress in older than in younger parents. In these same birds, we also found that stress‐induced maximum CORT levels decreased with age, which is consistent with what we have previously reported for this species. Measures of PRL and CORT were not, however, correlated within individuals. 6. Taken together, these results support the hypothesis that modulations of both the PRL and CORT stress response are flexible hormonal mechanisms that help to account for the increase in reproductive success that occurs with age.

Stress Response of Prolactin‐Releasing Peptide Knockout Mice as to Glucocorticoid Secretion

Prolactin-releasing peptide (PrRP) is known to have functions in prolactin secretion, stress responses, cardiovascular regulation and food intake suppression. In addition, PrRP-knockout (KO) male mice show obesity from the age of 22 weeks and increase their food intake. The plasma concentrations of insulin, leptin, cholesterol and triglyceride are also increased in obese PrRP-KO mice. Fatty liver, hypertrophied white adipose tissue, decreased uncoupling protein 1 mRNA expression in brown adipose tissue and glucose intolerance were observed in obese PrRP-KO mice. As we reported previously, PrRP stimulates corticotrophin-releasing factor and regulates the hypothalamic-pituitary-adrenal axis. Therefore, it is speculated that PrRP regulates both food intake and metabolism as a stress responses. In the present study, we compared blood glucose and plasma glucocorticoid concentrations in PrRP-KO mice, and found that PrRP-KO mice showed higher concentrations of blood glucose and corticosterone compared to wild-type mice after restraint stress. By contrast, there were no difference in c-Fos expression in the paraventricular hypothalamic nucleus and plasma adrenocorticotrophic hormone concentrations between the two groups. These results suggest that the different stress responses as to glucocorticoid secretion may be induced by different responses of the adrenal glands between wild-type and PrRP-KO mice. Thus, we conclude that PrRP-KO mice become obese as a result of increased food intake, a change in metabolism, and abnormal stress responses as to glucose concentration and glucocorticoid secretion.

Field study into the efficacy of a medicinal plant based complex for management of Equine Cushings Syndrome in ageing horses

Pituitary Pars Intermedia Dysfunction (PPID), known as Equine Cushings Syndrome, is characterized by elevated plasma glucocorticoid concentration due to adenoma or hyperplasia of the pars intermedia of the pituitary gland. Clinical signs include hirsutism, hyperhidrosis, muscle atrophy, chronic infections, polyuria, polydipsia and laminitis [1]. The dopamine agonist pergolide mesylate is the conventional therapy of choice. Compliance is poor due to expense, poor prognosis and adverse events [2].