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-releasing hormone (GnRH)-synthesizing neurons, or if their central inhibitory 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 intracerebroventricular (i.c.v.) delivery of GR agonists. Subcutaneous (s.c.) injection of the GR agonist, RU362 (2.5 mg/kg), promoted a significant reduction in circulating LH levels; pretreatment by i.c.v. injection of 1.0 microgram NALT, however, attenuated this inhibitory hormonal response. It was also found that rats treated sequentially with NALT and RU362 exhibited significantly lower plasma LH levels compared to rats injected with NALT alone. In other experiments, intracranial delivery of the synthetic glucocorticoid, dexamethasone (DEX), into either the ventricular system or the hypothalamic ARC resulted in significantly decreased plasma LH concentrations; the central inhibitory effects of DEX on peripheral LH release were reversed, however, by i.c.v. pretreatment with NALT. In summary, the present studies show that opioid receptor blockade attenuates systemic, as well as intracerebral inhibitory effects of GR agonists on the GnRH-pituitary LH axis, suggesting that circulating glucocorticoids inhibit LH, in part, through central actions involving endogenous opioid receptors. The observed decline in peripheral plasma LH following intra-ARC injection of DEX suggests that local GR may be functional target sites for glucocorticoid effects on LH.(ABSTRACT TRUNCATED AT 250 WORDS)
Briski
K P
KP
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, College of Veterinary Medicine, Washington State University, Pullman 99164-6520, USA.
Vogel
K L
KL
D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects; D003864:Depression, Chemical; D003907:Dexamethasone / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007267:Injections; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018847:Opioid Peptides / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D012636:Secretory Rate / Q000187:drug effects
D000732:Androstanols; D018847:Opioid Peptides; D011965:Receptors, Glucocorticoid; D011957:Receptors, Opioid; D007987:Gonadotropin-Releasing Hormone; D009270:Naloxone; D009271:Naltrexone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D003907:Dexamethasone; D007986:Luteinizing Hormone