ROLE OF ENDOGENOUS OPIOID-PEPTIDES IN CENTRAL GLUCOCORTICOID RECEPTOR(GR)-INDUCED DECREASES IN CIRCULATING LH IN THE MALE-RAT

While it has been shown that intracerebral administration of exogenous glucocorticoids diminishes pituitary luteinizing hormone (LH) release , it is not known if these hormones act directly on gonadotropin-relea sing hormone (GnRH)-synthesizing neurons, or if their central inhibito ry effects are mediated by specific neural substrates. In the present study, we examined whether the opioid receptor antagonist, naltrexone (NALT), alters patterns of LH release elicited by either systemic or i ntracerebroventricular (i.c.v.) delivery of GR agonists. Subcutaneous (s.c.) injection of the GR agonist, RU362 (2.5 mg/kg), promoted a sign ificant reduction in circulating LH levels; pretreatment by i.c.v. inj ection of 1.0 mu g NALT, however, attenuated this inhibitory hormonal response. It was also found that rats treated sequentially with NALT a nd RU362 exhibited significantly lower plasma LH levels compared to ra ts injected with NALT alone. In other experiments, intracranial delive ry of the synthetic glucocorticoid, dexamethasone (DEX), into either t he ventricular system or the hypothalamic ARC resulted in significantl y decreased plasma LH concentrations; the central inhibitory effects o f DEX on peripheral LH release were reversed, however, by i.c.v. pretr eatment with NALI. In summary, the present studies show that opioid re ceptor blockade attenuates systemic, as well as intracerebral inhibito ry effects of GR agonists on the GnRH-pituitary LH axis, suggesting th at circulating glucocorticoids inhibit LH, in part, through central ac tions involving endogenous opioid receptors. The observed decline in p eripheral plasma LH following intra-ARC injection of DEX suggests that local GR may be functional target sites for glucocorticoid effects on LH. Since i.c.v, administration of NALT reversed the inhibitory LH re sponse to these localized effects of DEX, opioid receptors may reside within neural pathways mediating the inhibitory effects of ARC GR on p ituitary LH.