β-Endorphin blocks luteinizing hormone-releasing hormone release by inhibiting the nitricoxidergic pathway controlling its release

Alicia G. Faletti, Claudio A. Mastronardi, Alejandro Lomniczi, Adriana Seilicovich, Martha Gimeno, Samuel M. Mccann, Valeria Rettori

    Research output: Contribution to journalArticle

    52 Scopus citations

    Abstract

    β-Endorphin blocks release of luteinizing hormone (LH)-releasing hormone (LHRH) into the hypophyseal portal vessels by stimulating μ-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 β-endorphin exerts its inhibitory action on this NOergic pathway, medial basal hypothalami (MBH) from male rats were incubated with β-endorphin (10-8 M). β-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 β- 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 μ-receptor antagonist, naltrexone (10-8 M). Not only was the inhibitory action of β-endorphin on LHRH and PGE2 release blocked by naltrexone (10- 8 M), but it increased NOS activity and LHRH and PGE2 release. β-Endorphin also stimulated γ-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 β- endorphin inhibits NP-induced PGE2 and LHRH release. The results indicate that β-endorphin stimulates μ-opioid receptors on NOergic neurons to inhibit the activation and consequent synthesis of NOS in the MBH. β- 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.

    Original languageEnglish (US)
    Pages (from-to)1722-1726
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume96
    Issue number4
    DOIs
    StatePublished - Feb 16 1999

    Keywords

    • Cyclooxygenase
    • Naltrexone
    • Nitric oxide synthase
    • Prostaglandin E
    • μ-Opiate receptor

    ASJC Scopus subject areas

    • General

    Fingerprint Dive into the research topics of 'β-Endorphin blocks luteinizing hormone-releasing hormone release by inhibiting the nitricoxidergic pathway controlling its release'. Together they form a unique fingerprint.

  • Cite this