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Regulation of the production of hypothalamic-pituitary-adrenal (HPA) axis secretagogues, corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), may be differentially sensitive to the negative feedback effects of glucocorticoids. We chose to study this phenomenon by examining the ability of dexamethasone to influence CRH and AVP heteronuclear RNA (hnRNA) levels in an escapable/inescapable (ES/IS) foot-shock stress paradigm. On Day 1, adult male rats were subjected to either ES or IS foot-shock; on Day 2, saline or dexamethasone (100 microg/kg) was administered 2 h prior to the stressor. We found that ES/IS foot-shock stimulated similar robust increases in plasma adrenocorticotrophic hormone (ACTH) and corticosterone concentrations, and medial parvocellular division of the paraventricular nucleus (mpPVN) AVP and CRH hnRNA and c-fos mRNA levels in saline-treated ES/IS rats. Dexamethasone pretreatment suppressed ACTH and corticosterone levels similarly in IS and ES animals. Dexamethasone pretreatment also suppressed mpPVN CRH and AVP hnRNA levels at 30 min. However, by 120 min, the mpPVN AVP hnRNA levels in dexamethasone-treated rats were similar to those measured in the saline group. We also found that rats that received the most shocks on Day 1 had greater HPA axis activation on Day 2. We conclude that the magnitude of the foot-shock stressor, determined by learned and immediate cues, is important in determining the magnitude of the HPA response.

There has been little research on effects of chronic stressors on neuroendocrine function in adolescence despite increasing evidence of enduring effects of stressors during this period on behaviour in adulthood. We previously reported that social stress (SS: daily 1 h isolation and new cage partner for 16 days) in adolescence altered locomotor responses to psychostimulants in adulthood. Here, we investigated neuroendocrine responses over the duration of the procedure that may underlie the enduring effects of SS. SS rats were compared to rats undergoing daily isolation only (ISO) and controls (CTL) to determine responses to acute and repeated isolation with and without social instability. At 30 days of age (first isolation), higher plasma corticosterone and corticotrophin-releasing hormone (CRH) mRNA expression in the paraventricular nucleus (PVN) of the hypothalamus and in the central nucleus of the amygdala (CeA) were found in males caged with a new partner (SS) after isolation than those returned to their original partner (ISO). On day 45, SS males and females showed less habituation (higher bioactive levels of corticosterone based on plasma corticosterone and corticosteroid binding globulin levels) to the 16th episode of isolation than did ISO. SS and ISO had higher baseline expression of CRH mRNA in the PVN on day 45 than did CTL, and only CTL had increased levels after isolation. CRH mRNA expression in the CeA increased to a first isolation in CTL and to a 16th isolation in SS but not in ISO males. Modest differences in social interactions were observed between SS and ISO when returned to their cages after isolation. The results suggest that mild social stressors in adolescence impede neuroendocrine adaptation to homotypic stressors. The resultant increase in exposure to glucocorticoids over adolescence may alter ongoing brain development and increase vulnerability to psychopathology.

Previous work has indicated that acute and repeated stress can alter thyroid hormone secretion. Corticosterone, the end product of hypothalamic-pituitary-adrenal (HPA) axis activation and strongly regulated by stress, has been suggested to play a role in hypothalamic-pituitary-thyroid (HPT) axis regulation. In the current study, we sought to further characterize HPT axis activity after repeated exposure to inescapable foot-shock stress (FS), and to examine changes in proposed regulators of the HPT axis, including plasma corticosterone and hypothalamic arcuate nucleus agouti-related protein (AGRP) mRNA levels. Adult male Sprague-Dawley rats were subjected to one daily session of inescapable FS for 14 days. Plasma corticosterone levels were determined during and after the stress on days 1 and 14. Animals were killed on day 15, and trunk blood and brains were collected for measurement of hormone and mRNA levels. Repeated exposure to FS led to a significant decrease in serum levels of 3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4). Stress-induced plasma corticosterone levels were not altered by repeated exposure to the stress. Despite the decrease in peripheral hormone levels, thyrotropin-releasing hormone (TRH) mRNA levels within the paraventricular nucleus of the hypothalamus were not altered by the stress paradigm. Arcuate nucleus AGRP mRNA levels were significantly increased in the animals exposed to repeated FS. Additionally, we noted significant correlations between stress-induced plasma corticosterone levels and components of the HPT axis, including TRH mRNA levels and free T4 levels. Additionally, there was a significant correlation between AGRP mRNA levels and total T3 levels. Changes in body weight were also correlated with peripheral corticosterone and TRH mRNA levels. These results suggest that repeated exposure to mild-electric foot-shock causes a decrease in peripheral thyroid hormone levels, and that components of the HPA axis and hypothalamic AGRP may be involved in stress regulation of the HPT., ((c) 2005 S. Karger AG, Basel)

The goal of this article is to describe some of the central nervous system circuits involved in the regulation of the hypothalamopituitary-adrenocortical (HPA) axis, with an emphasis on animal models believed to mimic the human experience of emotional stress. First, the basic constitutive elements of the HPA axis that control glucocorticoid secretion are reviewed. A description of the neural systems assumed to regulate the activity of the HPA axis, both anatomically and functionally, follows. It is argued that hypothalamic, septal and bed nucleus of the stria terminalis neurons are involved in the regulation of the HPA axis by situations eliciting emotional responses.

One day of fasting suppresses pulsatile LH secretion in adult male rhesus monkeys. In the present study, we determined whether the hypothalamic-pituitary-adrenal (HPA) axis is activated by 1 day of fasting, and if there is any evidence that an increase in the activity of the HPA axis causes the fasting-induced suppression of LH secretion. In the first experiment, blood samples were collected at 15-min intervals from nine monkeys for 24 h (0800-0800 h) on a day of normal feeding (animals fed a single daily meal at 1100 h) and again on a day of fasting (animals not fed their daily meal) to assess changes in LH and cortisol secretion caused by fasting. LH secretion on the day of fasting (4.44 +/- 0.85 LH pulses/24 h) was significantly suppressed compared to that on a day of normal feeding (7.67 +/- 0.74 LH pulses/24 h; P < or = 0.01), and there was a slight, but significant, rise in plasma cortisol levels from 17.86 +/- 2.29 to 25.14 +/- 2.74 micrograms/dl (measured at 1400 h) that was evident soon after the meal was missed on the day of fasting. However, within individual animals, there was no correlation between the rise in plasma cortisol levels and the decrease in LH secretion observed on a day of fasting (r = 0.37). A second experiment was performed to determine whether the small rise in plasma cortisol levels that occurred on a day of fasting was capable of suppressing LH secretion. Hydrocortisone acetate (HCA) was administered to six normally fed monkeys, creating a rise in plasma cortisol levels somewhat greater than the levels occurring during fasting (HCA treatment, 44.51 +/- 1.48 micrograms/dl; fasting, 18.42 +/- 1.62 micrograms/dl; measured between 1100-2400 h). However, HCA treatment had no effect on LH secretion, suggesting that the rise in cortisol that occurs during fasting does not cause LH suppression. To determine whether increased secretion of the neuropeptides that provide the central drive to the adrenal axis causes the suppression of LH secretion during fasting, six animals were treated with dexamethasone (0.25 mg/kg, im) on a day of fasting to inhibit the activity of the glucocorticoid-sensitive CRH neurons of the adrenal axis via increased glucocorticoid negative feedback. Dexamethasone treatment caused a marked suppression of circulating cortisol levels (to approximately 1.0 micrograms/dl), but it did not prevent the fasting-induced suppression of pulsatile LH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)