Y. Taché

Shift in adenohypophyseal activity during chronic intermittent immobilization of rats

Female rats were subjected to 8 h of daily immobilization for 1, 3, 6, 10 or 15 days. Exposure for 3 days inhibited b.w. and induced adrenal enlargement as well as thymus involution; 6 days of stress

Pattern of adenohypophyseal hormone changes in male rats following chronic stress.

To delineate the pattern of adenohypophyseal hormone secretion following chronic stress, adult male rats were exposed daily to 6 h of cold, forced exercise or immobilization for 3, 6, 10, 15, 28 or 42 consecutive days. Groups of these animals were sacrificed at the end of the last stress sessions, and plasma growth hormone (GH), luteinizing hormone (LH), prolactin (Prl) and follicle-stimulating hormone (FSH) levels were measured by radioimmunoassay (RIA). Irresspective of the different stimuli used, long-term stress induced a morphologic and hormonal response characterized by decreased ponderal growth, adrenal enlargement, thymus involution and significant diminutions in GH, Prl and LH levels with no modifications in FSH titers. The magnitude and duration of these changes varied with the severity of the stressors.

Hormonal modifications induced by chronic stress in rats

Abstract Chronic stress has a generally inhibitory effect on pituitary-gonadal function both in female and male rats inducing low circulating levels of LH, testosterone (T), prolactin (Prl) and, inconsistently, FSH. This inhibitory effect does not seem to be primarily due to pituitary dysfunction, since the adenohypophysis was capable of responding to exogenously administered LHRH and TRH, but is presumably the consequence of alterations of hypothalamic factor turnover. Testicular receptors to hCG were not modified by chronic stress which however induced a state of relative testicular hyper-responsiveness to hCG. Adrenal steroids seem to play a role both in the regulation of testicular hCG receptors and in chronic stress-induced Prl decrease, although further studies are needed to better characterize such a role.

Brain regulation of gastric acid secretion in rats by neurogastrointestinal peptides

Brain alteration of catecholaminergic, serotoninergic, dopaminergic, gabaergic and cholinergic pathways by intracisternal injection of agonists, antagonists or specific neurotoxic drugs did not significantly affect gastric acid secretion in 2 hr pylorus-ligated rats. In contrast, several neuropeptides were found to be very potent in influencing gastric secretion when administered intracisternally but not when given intravenously. Bombesin-like peptides, opioid peptides and arginine vasopressin acted within the brain to inhibit gastric acid secretion through yet unknown neurohumoral pathways, whereas TRH and some somatostatin analogs elicited brain stimulation of gastric acid output through vagal-dependent mechanisms. These observations have led to the concept that some specific neuropeptides may be important chemical messengers involved in physiologic brain processes regulating gastric acid secretion, and appear as new chemical probes to further investigate the brain-gut relationship.

CNS mediated inhibition of gastric secretion by bombesin: independence from interaction with brain catecholaminergic, and serotoninergic pathways and pituitary hormones

Abstract The effects of hypophysectomy and pharmacologic manipulation of brain biogenic amines on gastric secretion (volume and titratable acidity) and on CNS-mediated inhibition of gastric secretion by bombesin were studied in pylorus-ligated rats. Bombesin (100 ng), given intracisternally (i.c.), reduced the gastric secretory volume by 61%, raised pH values to 5 and virtually suppressed the titratable acidity of gastric secretion. Hypophysectomy did not modify the volume of secretion, lowered the gastric acid concentration by 37% and did not alter the magnitude of bombesins suppressive effect, suggesting that pituitary-derived substances do not participate in the expression of bombesins action. Depletion of brain catecholamines by combined administration of the neurotoxic agent 6-hydroxydopamine (400 μg twice, i.c.) and the catecholamine synthesis inhibitor α -methyl- p -tyrosine (250 mg/kg) or blockade of dopamine receptors by haloperidol (25 μg, i.c.), which induced a rise in plasma prolactin levels (indirect evidence of suppression of dopaminergic inhibitory tonus) neither modified gastric secretion nor the antisecretory effect of bombesin. Depletion of brain serotonin by the indolamine neurotoxin 5,6-dihydroxytryptamine (50 μg, i.c.) combined with p -chlorophenylalanine (315 mg/kg), an inhibitor of tryptophane-hydroxylase, did not affect gastric secretion or bombesins action. Administration of dopamine, serotonin or noradrenaline at 10-μg dose levels i.c. had no effect on gastric secretion. The demonstration that pharmacologic measures designed to interfere with the normal functioning of brain catecholaminergic and serotoninergic systems did not modify gastric secretion is not in favor of their involvement in the brain control of gastric secretion. Moreover, the fact that the potent antisecretory action of bombesin is not mimicked by, nor dependent upon, intact biogenic amine pathways further supports the concept that a direct neuropeptidergic pathway may participate in the CNS regulation of gastric secretion.

Role of Putative Neurotransmitters in Prolactin, GH and LH Response to Acute Immobilization Stress in Male Rats

Immobilization for 30 min induced a significant rise of prolactin (Prl), a significant reduction of growth hormone (GH), and no modification of plasma luteinizing hormone (LH) values in male rats. Depletion of brain catecholamine stores increased Prl and decreased LH levels while GH secretion was not affected. Blockade of beta-adrenergic receptors reduced GH and increased LH values. Plasma GH levels were also drastically reduced by depletion of brain serotonin (SER) levels and by atropine, and were increased by blockade of the H1 histamine (HIS) receptor. The anti-gamma-aminobutyric acid (GABA) agent picrotoxin significantly reduced Prl and GH plasma levels. Depletion of brain catecholamine stores or blockade of beta-adrenergic receptors antagonized the restraint-induced rise of plasma Prl values, while the decrease of GH elicited by stress was not modified by any pharmacological manipulation. These results indicate that although several putative neurotransmitters (PN) of the central nervous system (CNS) are implicated in the modulation of baseline levels of Prl, GH and LH, only the stress-induced activation of Prl secretion appears to be mediated by a PN, namely through a noradrenergic, beta-adrenergic route.

Effects of Chronic Stress on Pituitary Hormone Release Induced by Combined Hemi-Extirpation of the Thyroid, Adrenal and Ovary in Rats

Morphologic and hormonal changes, induced by combined ablation of a thyroid lobe, one adrenal and one ovary, were studied over a 15-day period in rats, some of whom were subjected to 8 h of daily immobilization. The compensatory hypertrophy (CH) of the contralateral glands in non-stressed animals was associated with a significant increase in the plasma levels of LH (from the 1st to the 10th day), prolactin (PRL, from the 3rd to the 6th day), FSH (on the 3rd day) and corticosterone (from the 6th to the 15th day), whereas GH titers were not altered. Immobilization for 1, 3, 6, 10 or 15 days inhibited the b.w. gain, induced involution of the thymus, enhanced compensatory enlargement of the adrenal, and blocked the CH of the ovary and, to a lesser degree, of the thyroid. This chronic stressor produced a marked rise in plasma corticosterone, antagonized the surge of PRL, FSH and LH, and decreased the plasma levels of GH. On the basis of these morphological and hormonal variations, it appears that severe chronic stress in hemi-thyroidectomized-adrenalectomized-ovariectomized animals further increases the ACTH response but antagonizes the increased secretion of the other pituitary hormones.

Adenohypophyseal Hormone Response to Chronic Stress in Dexamethasone-Treated Rats

The influence of dexamethasone treatment on the basal values of corticosterone, GH, prolactin (PRL), LH and FSH, as well as on the adenohypophyseal hormone response to chronic stress was studied in female rats. Dexamethasone acetate (25 micrograms/100 b.w.), given by gavage twice daily for 10 days, decreased the resting plasma levels of corticosterone, GH, LH and PRL, whereas the FSH titers remained normal. The secretion of ACTH (evaluated indirectly through corticosterone concentrations) and of GH appeared to be most sensitive to the suppressive effect of dexamethasone. The same hormonal response pattern was induced by 8 h of daily immobilization for 10 days, except that ACTH release was enhanced and the plasma LH titers dropped more drastically. Dexamethasone administration in combination with restraint did not alter the characteristic hormonal profile of chronic stress, despite the fact that ACTH secretion was completely blocked. These data suggest that the inhibition of PRL, LH and GH secretion following severe, chronic stress is not causally related to the sustained elevation of plasma ACTH.

Comparative studies on the effect of adrenocorticotrophic hormone (ACTH) and pregnenolone-16α-carbonitrile (PCN) upon drug response and distribution in rats

Abstract The effects of pretreatment with pregnenolone-16α-carbonitrile (PCN) or crystalline adrenocorticotrophic hormone (ACTH) and depot ACTH were investigated in female rats given picrotoxin, nikethamide, succinylcholine, strychnine, ethylmorphine, dioxathion, acetanilide, aniline, N -methylaniline, pancuronium, allopurinol, methyprylon, barbital, cyclobarbital, hexobarbital, phenobarbital, zoxazolamine, mephenesin, carisoprodol, sodium aurothiomalate or N -carbamoylarsanilic acid. Both ACTH and PCN offered significant protection against most of the drugs, but nikethamide and dioxathion toxicity was diminished solely by PCN, whereas that of aniline, N -methylaniline, barbital and phenobarbital was decreased by ACTH alone. Time-sequence studies revealed that a single injection of depot ACTH, or PCN gavage, 24 hr prior to zoxazolamine, significantly shortened paralysis. However, a few days of pretreatment with PCN were needed for maximal protection. ACTH, unlike the steroid, reduced zoxazolamine paralysis even in the presence of diethylaminoethyl-2,2-diphenylvalerate (SKF 525-A), a microsomal enzyme inhibitor. Protection by ACTH was not associated with decreased concentrations of zoxazolamine in blood, brain and muscle (syntoxic action). In contrast, PCN lowered the drug level, probably through increased biotransformation and/or excretion (catatoxic action). These findings furnish additional support to the view that catatoxic steroids mostly operate via the induction of drug-metabolizing enzymes in hepatic microsomes, while syntoxic agents augment resistance, probably through altered drug distribution, interactions at receptor sites or decreased receptor sensitivity.

Effect of Rat Stalk Median Eminence Extracts on Rat GH Secretion In vivo

Estradiol (0.2 mug), injected subcutaneously for 10 days to adult male rats, increased plasma growth hormone (GH) levels as compared with oil-treated controls. In estradiol-pretreated (10 days), urethane-anesthetized rats, the first as well as the second of two successive intracarotid injections, at 1-hour intervals, of one rat stalk median eminence equivalent evoked a significant rise in plasma radioimmunoassayable GH. Under the same conditions, cerebral cortex extracts (1 equivalent) induced a slight elevation whereas vasopressin (30 mU) or serotonin (200 ng) were ineffective. These results indicate that estrogen-primed, urethane-anesthetized rats can be used to demonstrate GH-releasing activity in rat SME extracts.