Stimulated Corticosterone Release Research Articles

Individual variation in natural or manipulated corticosterone does not covary with circulating glucose in a wild bird.

Animals respond to sudden challenges with a coordinated set of physiological and behavioral responses that enhance the ability to cope with stressors. While general characteristics of the vertebrate stress response are well described, it is not as clear how individual components covary between or within individuals. A rapid increase in glucocorticoids coordinates the stress response and one of the primary downstream results is an increase in glucose availability via reduced glucose utilization. Here, we asked whether between- and within-individual variation in corticosterone directly predict variation in glucose. We collected 2673 paired glucose and corticosterone measures from 776 tree swallows (Tachycineta bicolor) from four populations spanning the species range. In adults, glucose and corticosterone both increased during a standardized restraint protocol in all four populations. Moreover, in one population experimentally increasing a precursor that stimulates corticosterone release resulted in a further increase in both measures. In contrast, nestlings did not show a robust glucose response to handling or manipulation. Despite this group-level variation, there was very little evidence in any population that between-individual variation in corticosterone predicted between-individual variation in glucose regulation. Glucose was moderately repeatable within individuals, but within-individual variation in glucose and corticosterone were unrelated. Our results highlight the fact that a strong response in one aspect of the coordinated acute stress response (corticosterone) does not necessarily indicate that specific downstream components, such as glucose, will show similarly strong responses. These results have implications for understanding the evolution of integrated stress response systems.

Acute administration of GLP-1 receptor agonists induces hypolocomotion but not anxiety in mice.

Krass M, Rünkorg K, Vasar E, Volke V. Acute administration of GLP-1 receptor agonists induces hypolocomotion but not anxiety in mice.Objective: The aim of this study was to compare the behavioural and hormonal effects of systemic (subcutaneous) treatment with glucaemically equipotent doses of exenatide and liraglutide in mice.Methods: The effects of glucagon-like peptide-1 (GLP-1) receptor agonists were determined on anxiety level in the light–dark compartment test, the motor activity in automated activity cages and finally the forced swimming test was performed.Results: Both exenatide (1–20 µg/kg) and liraglutide (200–1200 µg/kg) decreased the glucose levels up to 30% in freely fed animals. In glucaemically equipotent doses the drugs induced very similar behavioural and hormonal effects: there was no change on anxiety level or immobility time, however, both drugs suppressed motor activity and increased corticosterone levels.Conclusion: We conclude that the two clinically approved GLP-1 receptor agonists induce very similar suppression of motor activity and stimulation of corticosterone release in mice.

Effects and Mechanisms of Nonylphenol on Corticosterone Release in Rat Zona Fasciculata-Reticularis Cells

Alkylphenol ethoxylate, consisting of ∼80% nonylphenol ethoxylate (NPEO), is a major group of nonionic surfactant. The primary degradation product of NPEO, nonylphenol (NP), interferes with reproduction, induces cell death in gonads, and leads to changes in other reproductive parameters. With such apparent stress, NP is believed to induce stress response mechanism, i.e., adrenal cortical hormone. However, the effects and action mechanisms of NP on rat adrenal zona fasciculata-reticularis (ZFR) cells are still unclear. This study explored the effects of NP on corticosterone release. ZFR cells were incubated with NP in the presence or absence of adrenocorticotropin (ACTH), 8-bromo-cyclic 3',5'-adenosine monophosphate (8-Br-cAMP), forskolin (FSK), 25-hydroxyl cholesterol (25-OH-cholesterol), pregnenolone, progesterone, or deoxycorticosterone at 37°C for 1 h. The concentrations of corticosterone or pregnenolone in the spent media were measured by radioimmunoassay. The expressions of steroidogenic acute regulatory (StAR) protein, cytochrome P450 side-chain cleavage (P450scc) protein, and 11β-hydroxylase in the cells were measured by Western blot. The data demonstrated that (1) NP stimulated corticosterone release induced by ACTH, 8-Br-cAMP, FSK, 25-OH-cholesterol, pregnenolone, progesterone, or deoxycorticosterone; (2) NP significantly increased pregnenolone release in the control, 25-OH-cholesterol, trilostane, and 25-OH-cholesterol + trilostane groups; (3) NP-stimulated corticosterone release was estrogen receptor dependent, but mediated by nitric oxide and p38 mitogen-activated protein kinase pathway independent; and (4) NP did not affect StAR, 11β-hydroxylase, or P450scc protein expression. These results suggest that NP acts directly on rat ZFR cells to stimulate corticosterone release and that the stimulation mechanism of NP mediates through post-cAMP corticosterone manufacture enzymes, i.e., P450scc and 11β-hydroxylase.

Feeding and drinking response following central administration of neuromedin S in chicks

Neuromedin S (NMS) is recognized as an anorexigenic peptide in the brain of mammals. In chicks ( Gallus gallus), however, the effect of NMS has not been investigated. Therefore, the purpose of the present study was to investigate whether intracerebroventricular (ICV) injection of NMS affected feeding and drinking behavior in chicks. The injection of NMS (0.01–1 nmol) significantly decreased food intake under both ad libitum and food deprivation-induced feeding conditions. However, NMS did not affect water deprivation-induced drinking behavior. ICV injection of NMS stimulated voluntary locomotion and wing-flapping behavior. In addition, we found that those effects of NMS might be related to the hypothalamus–pituitary–adrenal axis because ICV injection of NMS stimulated corticosterone release. The present study suggests that central NMS functions an anorexigenic factor in chicks.

Initial transference of wild birds to captivity alters stress physiology

Maintaining wild animals in captivity has long been used for conservation and research. While often suggested that captivity causes chronic stress, impacts on the underlying stress physiology are poorly understood. We used wild-caught chukar (Alectoris chukar) as a model avian species to assess how the initial 10 days of captivity alters the corticosterone (CORT) secretory pathway. In the first few days of captivity, birds lost weight, had lower hematocrit and demonstrated changes in CORT concentrations. Both baseline and restraint-stress-induced CORT concentrations decreased by days 3–5 of captivity and remained significantly lower throughout the 10 days although stress-induced concentrations began to recover by day 9. To delineate potential mechanisms underlying these CORT changes, we evaluated alterations to the hypothalamic–pituitary–adrenal (HPA) axis. Although chukar appear to be resistant to arginine vasotocin’s (AVT) effects on CORT release, adrenocorticotropin hormone (ACTH) stimulated CORT release; however, ACTH stimulation did not differ during the 10 days of captivity. In contrast, negative feedback axis sensitivity, as determined by both dexamethasone suppression as well as endogenous negative feedback, decreased by day 5 but was regained by day 9. In addition, the combined stressors of capture and long distance transport eliminated the animals’ ability to mount an acute CORT response on the day following the move. Therefore, introduction into captivity appeared to shift the chukar into a temporary state of chronic stress that began to recover within 9 days. The duration of these alterations likely varies due to differences in capture techniques, transport distance, and species studied.

Interleukin-6 and ACTH act synergistically to stimulate the release of corticosterone from adrenal gland cells

We investigated whether interleukin-6 (IL-6) could cause the release of corticosterone by a direct interaction with the adrenal gland. Primary cultures of rat adrenal glands were obtained by dispersion with collagenase and incubated for 24 h with different doses of IL-6. Levels of corticosterone were measured by competitive protein binding assay. A significant (P less than 0.025) dose-dependent increase in corticosterone levels was seen at all doses used. Time course experiments demonstrated that IL-6 stimulated corticosterone release over a period of 24 h but not after 12 or 3 h. The stimulation of adrenal cells with different doses of ACTH1-24 and 40 U/ml of IL-6 showed a synergistic effect when IL-6 was combined with low concentrations of ACTH1-24 (2 and 20 pmol/l). This effect was not evident at higher doses. Our results suggest that IL-6 may act at different levels of the hypothalmic pituitary adrenal axis. Moreover the finding of a synergistic effect with ACTH1-24 indicates that IL-6 could play a role in the long term response to stress.

Central administration of dipeptides, beta-alanyl-BCAAs, induces hyperactivity in chicks

BackgroundCarnosine (β-alanyl-L-histidine) is a putative neurotransmitter and has a possible role in neuron-glia cell interactions. Previously, we reported that carnosine induced hyperactivity in chicks when intracerebroventricularly (i.c.v.) administered. In the present study, we focused on other β-alanyl dipeptides to determine if they have novel functions.ResultsIn Experiment 1, i.c.v. injection of β-alanyl-L-leucine, but not β-alanyl-glycine, induced hyperactivity behavior as observed with carnosine. Both carnosine and β-alanyl-L-leucine stimulated corticosterone release. Thus, dipeptides of β-alanyl-branched chain amino acids were compared in Experiment 2. The i.c.v. injection of β-alanyl-L-isoleucine caused a similar response as β-alanyl-L-leucine, but β-alanyl-L-valine was somewhat less effective than the other two dipeptides. β-Alanyl-L-leucine strongly stimulated, and the other two dipeptides tended to stimulate, corticosterone release.ConclusionThese results suggest that central β-alanyl-branched chain amino acid stimulates activity in chicks through the hypothalamus-pituitary-adrenal axis. We named β-alanyl-L-leucine, β-alanyl-L-isoleucine and β-alanyl-L-valine as Excitin-1, Excitin-2 and Excitin-3, respectively.

Direct Effects of Prolactin on Adrenal Steroid Release in Male Hatano High-Avoidance (HAA) Rats May be Mediated Through Janus Kinase 2 (Jak2) Activity

Prolactin (PRL) has been proposed to directly stimulate corticosterone release. However, the role of PRL on adrenocortical function in male HAA rats has not been fully clarified. The aim of this study was to investigate the effect of PRL on the secretion of corticosterone and progesterone using an in vitro cell culture system in male rats. Administration of PRL (10(-7) and 10(-6) M) resulted in dose-dependent increases in corticosterone and progesterone release. Cotreatment with PRL produced an increase in the stimulatory effects of ACTH-induced corticosterone and progesterone secretion. However, the PRL-induced corticosterone and progesterone releases were significantly reduced by treatment with AG490, a specific Janus kinase 2 (Jak2) inhibitor. In addition, administration of AG490 blunted the significant inhibition of ACTH-induced corticosterone and progesterone secretion by PRL. These results demonstrated that PRL could act directly on the adrenal gland to drive corticosterone and progesterone secretion in male rats. Additionally, the results emphasize that PRL stimulation of adrenal steroid release may be mediated through Jak2 activity.

Seasonal changes in hypothalamic-pituitary-adrenal axis sensitivity in free-living house sparrows ( Passer domesticus)

Recent evidence indicates that house sparrows ( Passer domesticus) seasonally regulate corticosterone responses to capture, handling, and restraint. Responses during molt and in the fall are lower than responses in the winter and while breeding. This study tested whether changes in either adrenal tissue responsiveness to adrenocorticotropin (ACTH) or pituitary responsiveness to corticotropin releasing factor (CRF) or arginine vasotocin (AVT) could provide the mechanism regulating these seasonal changes. House sparrows were captured at two sites (Massachusetts and New Mexico, USA) and during the above four seasons and injected with exogenous ACTH, CRF, and AVT. ACTH stimulated further corticosterone release in all birds except Massachusetts birds in the winter, suggesting that reduced adrenal sensitivity to ACTH cannot explain reduced corticosterone release during fall and molt. However, exogenous ACTH was less effective during molt at both sites, implying that adrenal sensitivity does change. Pituitary sensitivity also changed seasonally, but these pituitary changes did not match the seasonal changes in corticosterone release. CRF and AVT only succeeded in elevating corticosterone in the spring in Massachusetts birds and in the winter in New Mexico birds, whereas CRF alone also stimulated corticosterone release in New Mexico birds in the fall. Taken together, these data indicate that house sparrows can alter the amount of corticosterone released from adrenal tissue, the amount of ACTH released from the pituitary, and the amount of CRF and AVT released from the hypothalamus, but that none of these changes correlate with seasonal changes in corticosterone release. Consequently, seasonal modulation of corticosterone release in house sparrows appear to result from a complicated mix of adrenal, pituitary, and hypothalamic changes that also vary seasonally.

The nociceptin receptor antagonist [Nphe1,Arg14,Lys15]nociceptin/orphanin FQ-NH2 blocks the stimulatory effects of nociceptin/orphanin FQ on the HPA axis in rats

Nociceptin/orphanin FQ (N/OFQ) is an opioid-related peptide that stimulates corticosterone release after i.c.v. administration in non-stressed rats. We employed in situ hybridization histochemistry to investigate N/OFQ–stimulated activation of the HPA axis at the hypothalamic and pituitary level. We have demonstrated that N/OFQ–induced activation of the HPA axis is mediated via the central N/OFQ peptide receptor (NOP) using the recently described selective NOP antagonist [Nphe1,Arg14,Lys15]nociceptin/orphanin FQ-NH2 (UFP-101).We found that, at 30 min post–i.c.v. injection, N/OFQ dose-dependently increased plasma adrenocorticotrophin hormone and corticosterone compared with the vehicle-injected controls. N/OFQ (1.0 μg) significantly increased CRF mRNA but not AVP mRNA within the parvocellular hypothalamic paraventricular nucleus compared with the control group, and significantly increased pro-opiomelanocortin (POMC) mRNA in the anterior pituitary. While UFP-101 (1.0 μg) alone had no significant effect on plasma corticosterone concentration it blocked the effect of N/OFQ (1.0 μg) on plasma corticosterone levels when compared with N/OFQ administered alone. UFP-101 also blocked the N/OFQ-induced increase in CRF mRNA and POMC mRNA. These results demonstrate that centrally administered N/OFQ activates the HPA axis via up-regulation of CRF and POMC mRNA and stimulation of corticosterone release in rats. Further, we have demonstrated for the first time that the selective NOP receptor antagonist UFP-101 blocks these effects indicating that N/OFQ–induced HPA axis activation is mediated via central NOP receptors.

Agouti Related Protein (AgRP) is Upregulated in Cushing's Syndrome

Alpha melanocyte-stimulating hormone (alpha-MSH) is an agonist at the melanocortin 3 (MC3-R) and melanocortin 4 (MC4-R) receptors. Alpha-MSH stimulates corticosterone release from rat and human adrenal cells. Patients with Cushing's syndrome have elevated levels of serum alpha-MSH. Agouti related protein (AgRP) is an endogenous antagonist at the MC3-R and MC4-R and is expressed in the rat adrenal cortex. AgRP antagonises alpha-MSH-induced corticosterone release from rat and bovine adrenal cells. This suggests that AgRP may have an inhibitory paracrine role in the adrenal gland. We measured adrenal AgRP mRNA expression and circulating AgRP in 2 patients with Cushing's syndrome and controls. Adrenal AgRP mRNA expression and plasma AgRP were higher in the patients with Cushing's syndrome compared to controls. Plasma AgRP in the patients with Cushing's syndrome following bilateral adrenalectomy and hydrocortisone replacement were similar to the levels seen in controls. Our results suggest that AgRP may have a novel inhibitory paracrine role in the human adrenal gland.

The rapid release of corticosterone from the adrenal induced by ACTH is mediated by nitric oxide acting by prostaglandin E2.

The adrenal cortex is a major stress organ in mammals that reacts rapidly to a multitude of external and internal stressors. Adrenocorticotropin (ACTH) is the main stimulator of the adrenal cortex, activating corticosteroid synthesis and secretion. We evaluated the mechanism of action of ACTH on adrenals of male rats, preserving the architecture of the gland in vitro. We demonstrated that both sodium nitroprusside (NP), a nitric oxide (NO) donor, and ACTH stimulate corticosterone release. NO mediated the acute response to ACTH because Nomega-nitro-l-arginine methyl ester, a NO synthase inhibitor, and hemoglobin, a NO scavenger, blocked the stimulation of corticosterone release induced by ACTH. NP stimulated prostaglandin E release, which in turn stimulated corticosterone release from the adrenal. Additionally, indomethacin, which inhibits cyclooxygenase, and thereby, prostaglandin release, prevented corticosterone release from the adrenal induced by both NP and ACTH, demonstrating that prostaglandins mediate acute corticosterone release. Corticosterone content in adrenals after incubation with ACTH or NP was lower than in control glands, indicating that any de novo synthesis of corticosterone during this period was not sufficient to keep up with the release of the stored hormone. The release induced by ACTH or NP depleted the corticosterone content in the adrenal by approximately 40% compared with the content of glands incubated in buffer. The mechanism of rapid release is as follows: NO produced by NO synthase activation by ACTH activates cyclooxygenase, which generates PGE(2), which in turn releases corticosterone stored in microvesicles and other organelles.

Agouti-related protein has an inhibitory paracrine role in the rat adrenal gland

α-Melanocyte-stimulating-hormone (α-MSH) is an agonist at the melanocortin 3 receptor (MC3-R) and melanocortin 4 receptor (MC4-R). α-MSH stimulates corticosterone release from rat adrenal glomerulosa cells in vitro. Agouti-related protein (AgRP) an endogenous antagonist at the MC3-R and MC4-R, is expressed in the adrenal gland. We investigated the expression of the MC3-R and MC4-R and the role of AgRP in the adrenal gland. MC3-R and MC4-R expression was detected in rat adrenal gland using RT-PCR. The effect of AgRP on α-MSH-induced corticosterone release was investigated using dispersed rat adrenal glomerulosa cells. AgRP administered alone did not affect corticosterone release, but co-administration of AgRP and α-MSH attenuated α-MSH-induced corticosterone release. To investigate glucocorticoid feedback, adrenal AgRP expression was compared in rats treated with dexamethasone to controls. AgRP mRNA was increased in rats treated with dexamethasone treatment compared to controls. Our findings demonstrate that adrenal AgRP mRNA is regulated by glucocorticoids. AgRP acting via the MC3-R or MC4-R may have an inhibitory paracrine role, blocking α-MSH-induced corticosterone secretion.

Orphanin FQ-induced hyperphagia is mediated by corticosterone and central glucocorticoid receptors

Orphanin FQ (Nociceptin) has been reported to stimulate food intake in satiated rats and to stimulate corticosterone release. A large body of evidence exists to link central feeding systems with the regulation of corticosterone. In this study, we sought to determine whether or not circulating corticosterone is necessary for the induction of food intake by Orphanin FQ. We found that intracerebroventricular injection of Orphanin FQ (0.64–5 nmoles) dose dependently stimulated food intake and plasma corticosterone within 30 min of injection. Removal of corticosterone, by adrenalectomy, abolished the hyperphagic effect of Orphanin FQ. The stimulatory effect of Orphanin FQ on food intake was still negated following a low dose of corticosterone replacement (corresponding to a plasma corticosterone concentration of 1.86±0.99 μg/dl). However, following a larger dose of corticosterone replacement (corresponding to a plasma corticosterone concentration of 8.92±0.55 μg/dl) the feeding effect was fully restored. We concluded this study by testing the glucocorticoid receptor antagonist, RU486 (Mifepristone, 80 μg/2 μl) on Orphanin FQ-induced feeding. Central injection of RU486, 30 min prior to injection of Orphanin FQ, significantly reduced Orphanin FQ-induced food intake in comparison to vehicle-treated controls. Overall, these data demonstrate the necessity for circulating corticosterone in the mediation of Orphanin-FQ-induced feeding and suggest that the mechanism through which the hyperphagic effect is obtained involves activation of central glucocorticoid receptors.

Studies on the involvement of histamine in the hypothalamic-pituitary-adrenal axis activation induced by nerve growth factor

Nerve growth factor (NGF) has been shown to stimulate the hypothalamic-pituitary-adrenocortical (HPA) axis. Since NGF induces the release of histamine from mast cells and in consideration of the fact that histamine is an HPA axis activator, we investigated whether NGF adrenocortical stimulation is mediated by histamine. To accomplish with it, the H 1 histamine antagonist promethazine and the H 2 antagonists metiamide and zolantidine were used in freely-moving cannulated rats. The increase in plasma corticosterone concentration induced by histamine administration was prevented completely by promethazine pretreatment but was unaffected by the H 2 antagonists. Neither H 1 nor H 2 antagonists affected the adrenocortical stimulation induced by NGF administration. Moreover, since mast cells are reportedly present in the rat adrenal gland and the locally released histamine mediates the release of adrenaline which, in turn, stimulates glucocorticoid synthesis and secretion, we studied the effect of NGF on basal and ACTH-stimulated corticosterone release from in vitro isolated quartered adrenal glands and collagenase-dispersed adrenal cells. The results from these in vitro experiments have indicated that NGF modified neither spontaneous nor stimulated corticosterone release. Altogether these observations suggest that endogenous histamine is unlikely to be involved in HPA axis stimulation by NGF and reinforce the previously proposed concept of an active participation of NGF in the control of adrenocortical activity.

Role of the Hypothalamic Pituitary Adrenal Axis and IL-6 in Stress-Induced Reactivation of Latent Herpes Simplex Virus Type 1

Hyperthermic stress induces reactivation of herpes simplex virus type 1 (HSV-1) in latently infected mice and also stimulates corticosterone release from the adrenals via activation of the hypothalamic pituitary adrenal axis. In the present study, we tested the hypothesis that stress-induced elevation of corticosterone potentiates HSV-1 reactivation in latently infected mice. Because of the putative role of IL-6 in facilitating HSV-1 reactivation in mice, the effect of hyperthermic stress and cyanoketone treatment on IL-6 expression in the trigeminal ganglion was also measured. Preadministration of cyanoketone, a glucocorticoid synthesis inhibitor, blocked the stress-induced elevation of corticosterone in a dose-dependent manner. Furthermore, inhibition of corticosterone synthesis was correlated with reduced levels of HSV-1 reactivation in latently infected mice. Hyperthermic stress elicited a transient rise in IL-6 mRNA levels in the trigeminal ganglion, but not other cytokine transcripts investigated. In addition, there was a significant reduction in MAC-3+, CD8+, and DX5+ (NK cell marker) cells in the trigeminal ganglion of latent HSV-1-infected mice 24 h after stress. Cyanoketone blocked the stress-induced rise in IL-6 mRNA and protein expression in the trigeminal ganglion latently infected with HSV-1. Collectively, the results indicate that the activation of the hypothalamic pituitary adrenal axis plays an important role in stimulating IL-6 expression and HSV-1 reactivation in the trigeminal ganglion following hyperthermic stress of mice.

The central corticotropin-releasing factor and glucagon-like peptide-1 in food intake of the neonatal chick

Recently, we have reported that central administration of glucagon-like peptide-1 (GLP-1) strongly decreases food intake of chicks. The aim of this study was to elucidate whether suppressed food intake induced by the central injection of GLP-1 is mediated by activation of the hypothalamic-pituitary-adrenal axis. First, the effects of central administration of corticotropin-releasing factor (CRF) were investigated. Birds (2-day-old) were food-deprived for 3 h and then CRF or saline was injected intracerebroventricular (i.c.v.). CRF strongly inhibited food intake. Thereafter, effects of central CRF or GLP-1 on plasma corticosterone concentration were examined. CRF significantly stimulated corticosterone release, but GLP-1 did not alter plasma corticosterone concentration. These results suggest that CRF is a potent inhibitor of food intake in the chick, but the suppression of food intake induced by central GLP-1 may not be involved in the activation of hypothalamic-pituitary-adrenal axis.

Growth hormone secretagogues stimulate the hypothalamic-pituitary-adrenal axis and are diabetogenic in the Zucker diabetic fatty rat.

Besides stimulating GH release, some GH secretagogues also release ACTH and adrenal steroids. Several novel classes of potent GH secretagogues have recently been described, and we have now tested their ability to release corticosterone in conscious normal rats. All analogs that released GH also stimulated corticosterone release to some degree, though the relative effects on GH and corticosterone varied somewhat. The corticosterone responses for some analogs were in the range of those obtained with CRF (2 microg, iv), whereas closely related analogs inactive for GH release failed to release corticosterone. Activation of the hypothalamic-pituitary-adrenal axis with GH release by GHRPs could be a highly diabetogenic combination in susceptible individuals. Therefore, a potent GHRP pentapeptide analog (G7039, 100 microg/day, sc, bid) was given to young obese male Zucker diabetic fatty rats (ZDF, n = 8/group) for 24 days. Other groups received hGH (500 microg/day, sc, bid), recombinant human insulin-like growth factor (rhIGF)-1 (750 microg/day, sc, infusion) or excipient, alone or in combination. Both G7039 and hGH increased weight gain, markedly raised serum glucose (G7039, 542 +/- 37; hGH, 725 +/- 30; excipient, 330 +/- 57 mg/dl) and doubled insulin levels but had opposite effects on serum triglycerides (G7039, 1412 +/- 44; hGH 501 +/- 46; excipient 1058 +/- 73 mg/dl) and fat depot weights. In contrast, treatment with IGF-1, alone or in combination with hGH or G7039, improved the diabetic state and stimulated growth. Thus, both G7039 and hGH treatment stimulated growth in ZDF rats, but greatly worsened diabetes, unless IGF-1 was coadministered. Some of the effects ofG7039 could be explained by GH release, but the effects on blood lipids and body fat were not seen with hGH and may reflect the additional activation of the hypothalamic-pituitary-adrenal axis by the secretagogue. The magnitude of these adverse effects in the ZDF animals suggest that chronic administration of GHRP analogs with cortisol-releasing activity to obese or diabetes-prone individuals warrants careful evaluation.

P-3-5 - Adrenal gland enlargement resulting from hyperactivity of the pituitary-adrenocortical system in alcoholics

The control of hypothalamic-pituitary-adrenocortical (HPA) activity by opioids seems to involve stimulatory and inhibitory pathways. The purpose of the present study was to determine the acute and chronic effects of selective μ- and δ-opioid agonists, administered centrally (i.c.v.), on pituitary-adrenocortical activity in the rat. The μ-agonist DAGO ([D-Ala2,N-MePhe4,Glyol]enkephalin; 0.75 nmol i.c.v.) and the δ-agonist DPDPE ([D-Pen2.5enkephalin; 194 nmol i.c.v.) both stimulated corticosterone release when administered acutely. Chronic administration of DAGO and DPDPE resulted in the development of tolerance to their neuroendocrine effects. These data suggest that both μ- and δ-opioid receptors are involved in the regulation of HPA activity under physiological conditions and during opiate abuse.

Restraint-induced changes in serum luteinizing hormone, prolactin, growth hormone and corticosterone levels in rats: effect of superior cervical ganglionectomy.

From about 10 to 36 h after superior cervical ganglionectomy (SCGx), peripheral sympathetic nerve terminals in the median eminence degenerate, nerve ending content is released, and a transient period of increased postsynaptic activity ensues. After this time, an irreversible, paralytic phase is established in the denervated territory. The present experiment was undertaken to examine, at single points during the wallerian degeneration phase (24 h after SCGx) and during the paralytic phase (10 days after denervation), the participation of peripheral sympathetic nerves in restraint-stress-induced changes of circulating luteinizing hormone (LH), prolactin (PRL), growth hormone (GH) and corticosterone levels. During the wallerian degeneration phase, serum LH did not augment after stress, as it did in sham-operated controls. In the paralytic phase, the poststress increases in LH attained similar values in sham-operated and SCGx rats. Immobilization stress augmented PRL levels to a similar extent in sham-operated and SCGx rats either 24 h or 10 days after surgery. During the wallerian degeneration phase, a decrease in serum GH levels was found in unrestrained rats. Immobilization stress decreased GH levels to 5-12% of unrestrained values in sham-operated and SCGx rats at both examination time points after surgery. Rats studied 24 h after SCGx exhibited significantly augmented serum corticosterone levels and failed to show restraint-stress-induced stimulation of corticosterone release. In rats subjected to SCGx 10 days earlier, both basal and poststress levels of corticosterone did not differ from sham-operated controls.(ABSTRACT TRUNCATED AT 250 WORDS)