CENTRAL OPIOID RECEPTORS MEDIATE GLUCOPRIVIC INHIBITION OF PITUITARY LH-SECRETION

The present studies investigated the significance of glucoprivic metab olic signals, particularly those of central origin, to the regulation of pituitary luteinizing hormone (LH). Groups of gonadectomized (GDX) adult male rats were treated with 2-deoxy-D-glucose (2-DG), an inhibit or of glycolysis, by either intravenous (50, 100, or 200 mg/kg) or int racerebroventricular (5, 20, or 100 mu g/rat) administration. Systemic drug treatment caused a significant decrease in mean plasma LH levels compared with saline-treated controls. Intracerebroventricular admini stration of 2-DG was also efficacious in suppressing circulating LH; a nimals treated with either of the two highest doses of the drug exhibi ted a significant reduction in plasma LH. In vitro studies examined di rect effects of 2-DG on pituitary gonadotrope secretory activity. Expo sure of anterior pituitary tissue to 2-DG during short-term perfusion had no significant impact upon either basal or gonadotropin-releasing hormone-stimulated LH release. Finally, groups of GDX rats were pretre ated by intracerebroventricular administration of either the nonselect ive opioid receptor antagonist, naltrexone, or the selective mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA), before intraveno us injection of 2-DG. Both receptor antagonists were observed to atten uate the suppressive effects of 2-DG: on circulating LH in these anima ls. In summary, treatment of GDX rats with the glucose antimetabolite, 2-DG, decreased plasma LH, suggesting that metabolic signaling of cel lular glucose oxidation is of physiological importance to the regulati on of pituitary hormone secretion. Findings that plasma LH was diminis hed in animals treated intracerebroventricularly with 2-DG implicate c entral glucoprivic receptors in neuroendocrine mechanisms governing th e reproductive endocrine axis. Attenuation of 2-DG-induced decreases i n circulating LH by opioid receptor antagonists suggests that these re ceptors, particularly the mu-subtype, mediate central effects of gluco privation on circulating LH.