Central opioid receptors mediate glucoprivic inhibition of pituitary LH secretion.
The present studies investigated the significance of glucoprivic metabolic 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 inhibitor of glycolysis, by either intravenous (50, 100, or 200 mg/kg) or intracerebroventricular (5, 20, or 100 microg/rat) administration. Systemic drug treatment caused a significant decrease in mean plasma LH levels compared with saline-treated controls. Intracerebroventricular administration of 2-DG was also efficacious in suppressing circulating LH; animals treated with either of the two highest doses of the drug exhibited a significant reduction in plasma LH. In vitro studies examined direct effects of 2-DG on pituitary gonadotrope secretory activity. Exposure 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 pretreated by intracerebroventricular administration of either the nonselective opioid receptor antagonist, naltrexone, or the selective mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA), before intravenous injection of 2-DG. Both receptor antagonists were observed to attenuate the suppressive effects of 2-DG on circulating LH in these animals. In summary, treatment of GDX rats with the glucose antimetabolite, 2-DG, decreased plasma LH, suggesting that metabolic signaling of cellular glucose oxidation is of physiological importance to the regulation of pituitary hormone secretion. Findings that plasma LH was diminished in animals treated intracerebroventricularly with 2-DG implicate central glucoprivic receptors in neuroendocrine mechanisms governing the reproductive endocrine axis. Attenuation of 2-DG-induced decreases in circulating LH by opioid receptor antagonists suggests that these receptors, particularly the mu-subtype, mediate central effects of glucoprivation on circulating LH.
Briski
K P
KP
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, College of Veterinary Medicine, Washington State University, Pullman 99164-6520, USA.
D000818:Animals; D001921:Brain / Q000502:physiology*; D003847:Deoxyglucose / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009919:Orchiectomy; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009271:Naltrexone; C024524:beta-funaltrexamine; D007986:Luteinizing Hormone; D003847:Deoxyglucose; D005947:Glucose