Prostaglandin E 2 release from astrocytes triggers gonadotropin-releasing hormone (GnRH) neuron firing via EP2 receptor activation

Jerome Clasadonte, Pierre Poulain, Naresh K. Hanchate, Gabriel Corfas, Sergio R. Ojeda, Vincent Prevot

    Research output: Contribution to journalArticlepeer-review

    61 Scopus citations

    Abstract

    Astrocytes in the hypothalamus release prostaglandin E 2 (PGE 2) in response to cell-cell signaling initiated by neurons and glial cells. Upon release, PGE 2 stimulates the secretion of gonadotropin-releasing hormone (GnRH), the neuropeptide that controls reproduction, from hypothalamic neuroendocrine neurons. Whether this effect on GnRH secretion is accompanied by changes in the firing behavior of these neurons is unknown. Using patch-clamp recording we demonstrate that PGE 2 exerts a dose-dependent postsynaptic excitatory effect on GnRH neurons. These effects are mimicked by an EP2 receptor agonist and attenuated by protein kinase A (PKA) inhibitors. The acute blockade of prostaglandin synthesis by indomethacin (INDO) or the selective inhibition of astrocyte metabolism by fluoroacetate (FA) suppresses the spontaneous firing activity of GnRH neurons in brain slices. Similarly, GnRH neuronal activity is reduced in mice with impaired astrocytic PGE2 release due to defective erbB signaling in astrocytes. These results indicate that astrocyte-to-neuron communication in the hypothalamus is essential for the activity of GnRH neurons and suggest that PGE 2 acts as a gliotransmitter within the GnRH neurosecretory system.

    Original languageEnglish (US)
    Pages (from-to)16104-16109
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume108
    Issue number38
    DOIs
    StatePublished - Oct 20 2011

    Keywords

    • Cyclooxygenase
    • Fertility
    • Glia-to-neuron signaling
    • Luteinizing hormone-releasing hormone
    • Preoptic region

    ASJC Scopus subject areas

    • General

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