期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：4
页码：1722-1726
DOI：10.1073/pnas.96.4.1722
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：{beta}-Endorphin blocks release of luteinizing hormone (LH)-releasing hormone (LHRH) into the hypophyseal portal vessels by stimulating {micro}-opiate receptors, thereby inhibiting secretion of LH. LHRH release is controlled by release of nitric oxide from nitricoxidergic (NOergic) neurons in the basal tuberal hypothalamus. To determine whether {beta}-endorphin exerts its inhibitory action on this NOergic pathway, medial basal hypothalami (MBH) from male rats were incubated with {beta}-endorphin (10-8 M). {beta}-Endorphin decreased basal secretion of LHRH, and significantly inhibited the release of prostaglandin E2 (PGE2), a known stimulant of LHRH release. Incubation of MBH with {beta}-endorphin at various concentrations (10-9-10-6 M) in vitro decreased the activity of NO synthase (NOS) (measured by the conversion of [14C]arginine to labeled citrulline). Conversely, the activity of NOS was increased by the {micro}-receptor antagonist, naltrexone (10-8 M). Not only was the inhibitory action of {beta}-endorphin on LHRH and PGE2 release blocked by naltrexone (10-8 M), but it increased NOS activity and LHRH and PGE2 release. {beta}-Endorphin also stimulated {gamma}-aminobutyric acid (GABA) release. Because GABA inhibits both nitroprusside (NP-induced PGE2 and LHRH release by blocking the activation of cyclooxygenase by NO, this is another mechanism by which {beta}-endorphin inhibits NP-induced PGE2 and LHRH release. The results indicate that {beta}-endorphin stimulates {micro}-opioid receptors on NOergic neurons to inhibit the activation and consequent synthesis of NOS in the MBH. {beta}-Endorphin also blocks the action of NO on PGE2 release and, consequently, on LHRH release, by stimulating GABAergic inhibitory input to LHRH terminals that blocks NO-induced activation of cyclooxygenase and consequent PGE2 secretion.
