Differential effect of corticosterone deficiency on the expression of LH, prolactin and insulin receptors on rat Leydig cells

The adverse effects of glucocorticoid deficiency on the expression of genes encoding Leydig cell surface receptors and the response to LH/prolactin/insulin to produce testosterone production are yet to be recognized. Following metyrapone-induced corticosterone deficiency, serum corticosterone, testosterone and insulin levels decrease, whereas serum prolactin exhibits a significant increase and serum LH remains unaltered. LH binding and LH receptor mRNA expression were not altered, but a significant decrease in PRL and insulin binding and in the mRNA expressions of their receptors were observed in corticosterone-deficient rats in vivo. Corticosterone deficiency significantly decreases the Leydig cellular basal as well as hormone-stimulated testosterone production in vitro. Simultaneous administration of corticosterone prevented its deficiency-induced changes in Leydig cells both in vivo and in vitro. Our results show that metyrapone-induced corticosterone deficiency impairs Leydig cell insulin and prolactin receptors, and their mRNA expression and the response of Leydig cells to LH/PRL/insulin on testosterone production.     

Circulating prolactin and corticosterone concentrations during the development of migratory condition in the Dark-eyed Junco, Junco hyemalis

Endogenous plasma prolactin and baseline corticosterone concentrations were measured in Dark-eyed Juncos (Junco hyemalis, n=27) photostimulated into migratory condition to look at how these hormones may be linked to the development of migratory condition. In addition to the commonly used assay for corticosterone, a recombinant-derived European starling prolactin assay validated for Dark-eyed juncos was used to measure endogenous prolactin in order to detect small but significant changes in plasma prolactin levels. In response to transfer from short (10.5L:13.5D) to long (18L:6D) days, the birds increased in body mass, fat score, daily food intake, and nocturnal migratory locomotor activity (Zugunruhe). On short-days, both hormones were low (corticosterone mean=2.89ng/mL+/-0.48 SE; prolactin mean=6.43ng/mL+/-1.31 SE). But, within 14 days of photostimulation both hormones increased significantly (Day 14: corticosterone mean=5.71ng/mL+/-0.77 SE; prolactin mean=19.67ng/mL+/-2.81 SE), rising further by Day 48 (corticosterone mean=8.41ng/mL+/-0.72; prolactin mean=112.67ng/mL+/-9.18 SE). On Day 48, birds with the most fat (fat score=3) had significantly higher corticosterone levels than those with less fat (fat score=2). This pattern, albeit not statistically significant, was similar for prolactin. These results illustrate that, independent of the seasonal peak in prolactin associated with the onset of photorefractoriness, plasma prolactin levels can rise, in concert with corticosterone, as birds come into spring migratory condition, providing some support for earlier hypotheses that these two hormones play an integral role in the development of migratory condition. Whether similar changes in plasma prolactin occur with respect to autumn migration, as does baseline corticosterone, has yet to be determined.     

Postnatal handling does not attenuate hypothalamic-pituitary-adrenal hyperresponsiveness after prenatal ethanol exposure

BACKGROUND: Prenatal ethanol exposure results in hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stress in the adult animal. In contrast, an early environmental manipulation, termed "postnatal handling," has been shown to result in decreased and/or less prolonged HPA activity in response to moderate stressors throughout the lifespan of the animal. The effects of both prenatal ethanol exposure and postnatal handling on HPA activity may be mediated by altered feedback regulation of the HPA axis. The present study tested the hypothesis that postnatal handling could attenuate the impact of prenatal ethanol exposure on hormonal responses to stressors. METHODS: Male and female Sprague Dawley rats from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) groups were either handled (H) or nonhandled (NH) during the preweaning period and were tested at 4 to 5 months of age. Animals were subjected to a 60 min restraint stress, 3 hr after intraperitoneal injection with either saline (SAL) or a synthetic glucocorticoid, dexamethasone-21-phosphate (DEX), in order to examine HPA responsiveness after DEX blockade of endogenous HPA activity. Blood samples were collected via jugular cannulae immediately before restraint (0 min), during restraint (10, 30, and 60 min), and 30 min after the termination of restraint (90 min). RESULTS: For both males and females, DEX administration significantly reduced plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations compared with SAL administration. H animals showed greater suppression of HPA activity (i.e., lower ACTH and/or CORT levels) than NH animals regardless of prenatal group. In addition, E females from both the H and NH treatments showed elevated ACTH and CORT after both SAL and DEX administration, whereas H and NH E males showed elevations in ACTH and CORT only after SAL, compared with their PF and C counterparts. CONCLUSIONS: These data extend results from previous studies that demonstrated HPA hyperresponsiveness in E animals. The finding that E females but not males exhibit elevated ACTH and CORT after DEX administration suggests that prenatal ethanol exposure results in sex-specific alterations of HPA feedback. Consistent with previous data, handling in itself reduced the HPA response to restraint stress. However, handling did not attenuate either HPA hyperresponsiveness or feedback deficits in E animals.     

Circadian rhythms in the hypothalamo-pituitary-adrenal (HPA) axis

The pronounced daily variation in the release of adrenal hormones has been at the heart of the deciphering and understanding of the circadian timing system. Indeed, the first demonstration of an endocrine day/night rhythm was provided by Pincus (1943), by showing a daily pattern of 17-keto-steroid excretion in the urine of 7 healthy males. Twenty years later the adrenal gland was one of the very first organs to show, in vitro, that circadian rhythmicity was maintained. In the seventies, experimental manipulation of the daily corticosterone rhythm served as evidence for the identification of respectively the light- and food-entrainable oscillator. Another 20 years later the hypothalamo-pituitary-adrenal (HPA)-axis was key in furthering our understanding of the way in which rhythmic signals generated by the central pacemaker in the hypothalamic suprachiasmatic nuclei (SCN) are forwarded to the rest of the brain and to the organism as a whole. To date, the adrenal gland is still of prime importance for understanding how the oscillations of clock genes in peripheral tissues result in functional rhythms of these tissues, whereas it has become even more evident that adrenal glucocorticoids are key in the resetting of the circadian system after a phase-shift. The HPA-axis thus still is an excellent model for studying the transmission of circadian information in the body.     

Effects of prenatal ethanol exposure on hypothalamic-pituitary-adrenal responses to chronic cold stress in rats

Animals prenatally exposed to ethanol typically exhibit hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stressors. In contrast to previous studies that have investigated effects of prenatal ethanol exposure on HPA responses to acute or intermittent stressors, our study investigated HPA responses to a chronic continuous stressor, cold stress (4 degrees C for 0, 1, or 3 days). We tested the hypothesis that prenatal ethanol exposure would result in increased plasma corticosterone (CORT) and adrenocorticotropin (ACTH) responses and increased peptide [corticotropin-releasing factor and vasopressin] mRNA levels in the paraventricular nucleus (PVN) of the hypothalamus compared to that in control animals. In addition, CORT and ACTH responses were measured after exposure to an acute stressor (i.p. isotonic saline injection), superimposed during chronic cold exposure, to examine possible sensitization of the HPA response to the acute stress. Thus, blood samples were collected at the end of each of the three periods of cold exposure, either before (0 min) or 15 min after acute stress. The subjects were adult male and female Sprague-Dawley rat offspring from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) treatment groups. Exposure to cold stress resulted in significant body weight loss in E males at 1 day and in both males and females of all prenatal treatment groups by 3 days of cold stress. Males in all prenatal groups also exhibited significant increases in adrenal weight:body weight ratios. Cold stress alone (0 min condition) increased CORT levels in E males and overall ACTH levels in E males and females compared to controls. ACTH levels were also higher overall in E compared to control males after acute stress (15 min condition). Sensitization of the CORT response to acute stress was observed in males but not females across all prenatal treatment groups. Corticotropin-releasing factor and vasopressin mRNA levels in the PVN were not significantly affected by prenatal treatment or chronic cold stress in either males or females. In contrast, both males and females displayed increases in PVN thyrotropin-releasing hormone (TRH) mRNA levels after cold stress. These data support and extend previous work demonstrating differential effects of prenatal ethanol exposure on HPA responsiveness of male and female offspring, and suggest that E males may be more vulnerable to the effects of chronic cold stress than E females.     

Behavioral and neural trade-offs between song complexity and stress reaction in a wild and a domesticated finch strain

The Bengalese finch is the domesticated strain of the wild white-rumped munia. Bengalese finches have been domesticated and reproductively isolated for over 250 years from the wild strain. During this period, the courtship songs of the domesticated birds became phonologically and syntactically complex. In addition, psychological and physiological stress reactions to environmental and social factors diverged between the two strains. Based on our behavioral and histological studies, we consider the balance between the glucocorticoid- and mineralocorticoid receptors in song control nuclei and in the avian amygdala as to determine whether a bird can develop complex songs or rather has to devote the neural resources for the maintenance of stress reactions. We therefore suggest that phonological and syntactical complexity in Bengalese finch songs initially evolved because domestication freed them from species recognition and environmental stress, and then sexual selection increased the complexity. Neural and molecular studies also support the notion that Bengalese finches keep more song plasticity as adults. In conclusion, the present study suggests that domestication changed factors related with psychobiology of stress reactions and learning in finches.     

逍遥丸对皮质酮诱导小鼠抑郁样行为的干预机制※

目的:观察逍遥丸对皮质酮诱导小鼠抑郁样行为的干预作用,并探讨其分子机制。方法:将50只ICR雄性小鼠,随机分为5组:正常组、皮质酮模型组、阳性对照氟西汀组(20 mg/kg)、低剂量逍遥丸(200 mg/kg)组、高剂量逍遥丸组(600 mg/kg),通过皮下注射皮质酮诱导小鼠抑郁模型。持续35天后,采用糖水偏好实验和强迫游泳实验评价动物抑郁样行为;采用ELISA方法测小鼠血清中皮质酮含量及小鼠海马组织中脑源性神经营养因子(BDNF)的含量。结果:皮质酮可以降低糖水偏好值、增加小鼠强迫游泳的不动时间,而逍遥丸可以显著提高糖水偏好值、减少小鼠不动时间;长期注射皮质酮可增加血清皮质酮水平,降低海马组织中BDNF含量,而逍遥丸可以降低小鼠血清中皮质酮的含量并且能够提高海马组织中BDNF含量。结论:逍遥丸可以有效降低小鼠血清中皮质酮的含量并增加小鼠海马中BDNF含量,改善神经营养系统,产生抗抑郁样作用。     

Adrenocortical function of Arctic-breeding glaucous gulls in relation to persistent organic pollutants

Unpredictable changes in the environment stimulate the avian hypothalamo-pituitary-adrenal axis to produce corticosterone, which induces behavioural and metabolic changes that enhance survival in the face of adverse environmental conditions. In addition to profound environmental perturbations, such as severe weather conditions and unpredictable food shortages, many Arctic-breeding birds are also confronted with chronic exposure to persistent organic pollutants (POPs), some of which are known to disrupt endocrine processes. This study investigated the adrenocortical function of a top predator in the Arctic marine environment, the glaucous gull (Larus hyperboreus). High concentrations of organochlorines, brominated flame retardants and metabolically-derived products in blood plasma of incubating glaucous gulls were associated with high baseline corticosterone concentrations in both sexes and a reduced stress response in males. Contaminant-related changes in corticosterone concentration occurred over and above differences in body condition and seasonal variation. Chronically high corticosterone concentrations and/or a compromised adrenocortical response to stress can have negative effects on the health of an individual. The results of the present study suggest that exposure to POPs may increase the vulnerability of glaucous gulls to environmental stressors and thus could potentially compromise their ability to adapt to the rapidly changing environmental conditions associated with climate change that are currently seen in the Arctic.