The implication of opiates in the glucocorticoid-mediated inhibition of LH secretion in rats

Belhadj, H.; Besi, L. De; Bardin, C. Wayne; Thau, Rosemarie B.

doi:10.1677/joe.0.1220451

Cited by 14 publications

(7 citation statements)

References 30 publications

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“…Current findings suggest that EOP involvement may depend upon the nature and/or severity of the chronic stress stimulus, since opioid receptor antagonism can reverse chronic sur gical-[5], but not chronic restraint stress-induced de creases in circulating LH [37], The coexistence of GR with P-END [38] and CRF immunoreactivity [39][40][41] supports the possibility of a modulatory impact of gluco corticoids on neurons synthesizing these neuropeptides. Observations that DEX-induced decreases in plasma LH are reversed by opioid receptor antagonists [42,43] strengthen the hypothesis that proopiomelanocortin (POMC) peptide-producing neurons may function as neu ral substrates for central inhibitory effects of glucocorti coids on the GnRH-pituitary LH axis. Glucocorticoids also promote negative feedback inhibition of CRF synthe sis [44,45] and release [46] by paraventricular neurons.…”

Section: Discussionmentioning

confidence: 74%

The Antiglucocorticoid, RU486, Attenuates Stress-Induced Decreases in Plasma-Luteinizing Hormone Concentrations in Male Rats

Briski¹,

Vogel²,

Mclntyre³

1995

Neuroendocrinology

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The present studies investigated the role of glucocorticoid receptors (GR) in the inhibitory effects of acute and chronic immobilization stress on pituitary luteinizing hormone (LH) release. Systemic administration of the GR antagonist, RU486, significantly attenuated the acute decline in circulating LH observed in intact male rats immobilized by encasement within paper cocoons. Whereas vehicle-injected controls exhibited a significant reduction in plasma LH between +1 and +5 h of stress, animals given subcutaneous (sc) injections of 2.5 mg RU846/kg did not exhibit a reduction in circulating LH until 4 h after initiation of stress. Plasma LH levels in the GR-treated group were significantly elevated compared to the vehicle controls between +1 and +3 h of stress. Repetitive exposure to the same stress stimulus 24 and 48 h later resulted in decreased plasma LH levels in the vehicle-treated rats, but not in the animals injected sc with RU486. Other studies showed that intracere-broventricular (icv) administration of RU486 (10.0 µg/rat) also blunted the inhibitory effects of acute and chronic immobilization stress on pituitary LH release. In experiments designed to evaluate whether activation of central GR can influence the magnitude and/or temporal characteristics of the LH secretory response to acute inhibitory stress, it was observed that animals pre-treated by icv injection of the GR agonist, RU362, exhibited a greater reduction in plasma LH levels during the first hour of stress, as compared to rats pretreated with vehicle alone.

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Section: Discussionmentioning

confidence: 74%

The Antiglucocorticoid, RU486, Attenuates Stress-Induced Decreases in Plasma-Luteinizing Hormone Concentrations in Male Rats

Briski¹,

Vogel²,

Mclntyre³

1995

Neuroendocrinology

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“…An alternative possibil ity is that glucocorticoid effects on GnRH may be me diated by neuropeptidergic and/or monoaminergic neu rons; in fact, GR-like immunoreactivity has been local ized within nuclei of arcuate neurons immunolabeled for p-endorphin [62], neuropeptide Y [63,64], or dopamine [65]. Indeed, it has been reported that blockade of opiate receptors by nalmefene can prevent decreases in plasma LH observed 30 min after s.c. injection of DEX [8].…”

Section: Discussionmentioning

confidence: 99%

“…Specific receptors for these hormones have been detected within the anterior pituitary and central nervous system (CNS) [10][11][12][13][14][15][16][17][18], Al though glucocorticoids have been shown to exert diver gent effects on basal and/or gonadotropin-releasing hor mone (GnRH)-stimulated LH release in vitro by primary pituitary cell cultures [19][20][21][22][23], studies involving adminis tration of these steroids to pituitary tissue during short term perifusion have yielded more consistent results, in that glucocorticoids were found to have no effect upon basal LH, but to inhibit hormone release in response to GnRI I [9,23]. Although most reports indicate that gluco corticoids suppress pituitary responsiveness to an exoge nous GnRH challenge in vivo [4,5,7,9,24], steroid treat ment has been shown, under certain circumstances, to suppress plasma LH levels in vivo, without altering pitu itary GnRH receptor number or GnRH-induced LH release [7,8,[25][26][27], These latter observations lend sup port for a neural site(s) of inhibitory glucocorticoid ac tion.…”

Section: Introductionmentioning

confidence: 99%

“…Female rats exhibit deviations of estrous cyclicity follow ing implantation of cortisol [4], as well as an attenuation of the preovulatory luteinizing hormone (LH) surge in response to treatment with cortisol or the potent synthetic glucocorticoid, dexamethasone (DEX) [4,5]. Basal LH release in vivo in rats of both sexes is suppressed by CORT [6], the predominant endogenous glucocorticosteroid in rats, or DEX [5,[7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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Antagonism of Type II, but Not Type I Glucocorticoid Receptors Results in Elevated Basal Luteinizing Hormone Release in Male Rats

Briski

Sylvester²

1994

Neuroendocrinology

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The present studies utilized a phaimacologic approach to evaluate the role of corticosterone-preferring mineralocorticoid receptors (type I or MR) versus classic glucocorticoid receptors (type II or GR) in the regulation of basal pituitary luteinizing hormone (LH) secretion in vivo in male rats. Animals bearing indwelling intracardiac venous catheters received a subcutaneous (s.c.) injection of either vehicle, the MR antagonist, RU 752 (0.5 or 5.0 mg/kg body weight), or the GR antagonist, RU 486 (0.5 or 5.0 mg/kg body weight). Additional groups of rats were implanted with indwelling intracerebroventricular (i.c.v.) cannulas and intravenous catheters for drug administration and blood withdrawal, respectively, and injected i.c.v. with vehicle or graded doses (0.1, 1.0 or 10.0 µg/rat) of RU 752 or RU 486. The MR RU 752 failed to alter plasma LH concentrations regardless of dose or route of administration. In contrast, the GR antagonist, RU 486, elicited significant, dose-dependent increases in circulating LH when given either s.c. or i.c.v. Animals injected s.c. with either 0.5 or 5.0 mg RU 486/kg body weight showed elevated plasma LH levels; while the magnitude of this secretory response was not different between the two drug-treated groups, hormone levels remained elevated over baseline for a longer period of time in rats given the higher dose. Central administration of RU 486 at a dose of either 1.0 or 10.0 µg also resulted in elevated LH release; both the magnitude and duration of this increase in plasma LH were dose-dependent. In additional experiments, groups of rats were pretreated with vehicle or the synthetic GR agonist, RU 362, before administration of RU 486. These studies showed that the stimulatory effect of RU 486 on peripheral LH was abolished by prior interaction of GR with the exogenous ligand. In summary, the ability of the GR antagonist, RU 486, to promote an increase in plasma LH concentrations in intact male rats suggests that endogenous glucocorticoids exert a tonic inhibitory tonus on in vivo LH release in these animals, and that GR mediate these suppressive effects. Observations that drug-induced elevations in circulating LH were abolished by pretreatment with the GR agonist, RU 362, suggest that the stimulatory effects of RU 486 on hormone release were achieved by an antiglucocorticoid action. The current findings that plasma LH was increased following intracranial administration of RU 486 implicate central GR in neuroendocrine mechanisms governing pituitary LH.

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“…Opioids are known to inhibit the reproductive axis. In the rat, dexamethasone reduces the postcastration rise in LH and opioid antagonists reverse the glucocorticoid-inhibiting effect on LH [15]. A recent study with rats [16]showed that the LH suppression obtained by intracerebroventricular and systemic administration of dexamethasone was blocked by pretreatment with naltrexone.…”

Section: Introductionmentioning

confidence: 99%

Effects of Dexamethasone and Dexamethasone plus Naltrexone on Pituitary Response to GnRH and TRH in Normal Women

Marca

Torricelli²,

Morgante³

et al. 1999

Horm Res Paediatr

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The hypothesis that glucocorticoids have a direct central inhibitory effect on the reproductive axis is sutained by the identification of glucocorticoid receptors on GnRH-secreting neurons and gonadotropic pituitary cells. It has been proposed that glucocorticoids and opioids interact centrally in the regulation of the GnRH-LH axis. The inhibitory effect of glucocorticoids may manifest not only directly through the hormone-receptor link, but also indirectly through an increase in opioid tone. The aim of this study was to evaluate the role of glucocorticoids and glucocorticoids combined with an opioid antagonist, in the regulation of basal and GnRH- and TRH-stimulated secretion of LH, FSH and Prl in 7 women with normal menstrual cycles. Blood samples were obtained every 10 min for an hour. GnRH (50 μg) and TRH (200 μg) were administered and blood sampling was continued every 15 min for 2 h (day 1). At 5 a.m. the next day, naltrexone (50 mg) was given and at 8 a.m. the GnRH-TRH test was repeated (day 2). At 5 a.m. on day 3, the patients took 2 mg oral dexamethasone and the test was repeated. At 5 a.m. on day 4, the patients took naltrexone and dexamethasone and at 8 a.m. the GnRH-TRH test was repeated. Administration of naltrexone did not cause significant changes in basal concentrations of LH and FSH and their response to GnRH. The area under the curve of the LH response to GnRH on day 3 was significantly less than on days 1, 2 and 4. Administration of naltrexone (day 2) did not cause any significant increase in basal and TRH-stimulated levels of Prl with respect to day 1. On day 3, dexamethasone caused a reduced response of Prl to TRH. Pretreatment with naltrexone (day 4) prevented this reduction. These results suggest that suppression of the response of LH to GnRH induced by dexamethasone may be partly mediated by endogenous opioids. Dexamethasone led to a reduction in the response of Prl to TRH, and naltrexone blocked this suppression. Hence the suppression of Prl and LH by dexamethasone must be partly mediated by endogenous opioids, which must therefore inhibit pituitary secretion of Prl.

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The implication of opiates in the glucocorticoid-mediated inhibition of LH secretion in rats

Cited by 14 publications

References 30 publications

The Antiglucocorticoid, RU486, Attenuates Stress-Induced Decreases in Plasma-Luteinizing Hormone Concentrations in Male Rats

The Antiglucocorticoid, RU486, Attenuates Stress-Induced Decreases in Plasma-Luteinizing Hormone Concentrations in Male Rats

Antagonism of Type II, but Not Type I Glucocorticoid Receptors Results in Elevated Basal Luteinizing Hormone Release in Male Rats

Effects of Dexamethasone and Dexamethasone plus Naltrexone on Pituitary Response to GnRH and TRH in Normal Women

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