Inhibitory pathways and the inhibition of luteinizing hormone-releasing hormone release by alcohol

Alejandro Lomniczi, Claudio A. Mastronardi, Alicia G. Faletti, Adriana Seilicovich, Andrea De Laurentiis, Samuel M. McCann, Valeria Rettori

    Research output: Contribution to journalArticle

    29 Scopus citations

    Abstract

    In this research we examined the mechanisms by which ethanol (EtOH) inhibits luteinizing hormone-releasing hormone (LHRH) release from incubated medial basal hypothalamic explants. EtOH (100 mM) stimulated the release of two inhibitory neurotransmitters: γ-aminobutyric acid (GABA) and γ- endorphin. EtOH also inhibited NO production, indicative of a suppression of nitric oxide synthase (NOS) activity. This inhibition was reversed by naltroxone (10-8 M), a μ-opioid receptor blocker, indicating that the inhibition of NOS by EtOH is mediated by β-endorphin. EtOH also blocked N- methyl-D-aspartic acid-induced LHRH release, but the blockade could not be reversed by either the GABA receptor blocker, bicuculline (10-5 M), naltroxone (10-8 M), or both inhibitors added together. However, increasing the concentration of naltrexone (10-6 M) but not bicuculline (10-4 M) reversed the inhibition. When we lowered the concentration of EtOH (50 mM), the EtOH-induced blockade of LHRH release could be reversed by either bicuculline (10-5 M), naltroxone (10-8 M), or the combination of the two blockers. Therefore, GABA is partially responsible for the blockade of N- methyl-D-aspartic acid-induced LHRH release. The block by GABA was exerted by inhibiting the activation of cyclooxygenase by NO, because it was reversed by prostaglandin E2, the product of activation of cyclooxygenase. Because the inhibition caused by the higher concentration of EtOH could not be reduced by bicuculline (10-4 M) but was blocked by naltroxone (10-6 M), the action of alcohol can be accounted for by stimulation of β-endorphin neurons that inhibit LHRH release by inhibition of activation of NOS and stimulation of GABA release.

    Original languageEnglish (US)
    Pages (from-to)2337-2342
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume97
    Issue number5
    DOIs
    StatePublished - Feb 29 2000

    Keywords

    • Bicuculline
    • Cyclooxygenase
    • Naltrexone
    • Nitric oxide synthase
    • Prostaglandin E

    ASJC Scopus subject areas

    • General

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