Inhibitory action of gonadotropin-inhibitory hormone on the signaling pathways induced by kisspeptin and vasoactive intestinal polypeptide in GnRH neuronal cell line, GT1-7

You Lee Son, Takayoshi Ubuka, Tomoko Soga, Kazutoshi Yamamoto, George E. Bentley, Kazuyoshi Tsutsui

    Research output: Contribution to journalArticle

    21 Citations (Scopus)

    Abstract

    Gonadotropin-inhibitory hormone (GnIH) acts as a negative regulator of reproduction by acting on gonadotropes and gonadotropin-releasing hormone (GnRH) neurons. Despite its functional significance, the molecular mechanism of GnIH action in the target cells has not been fully elucidated. To expand our previous study on GnIH actions in gonadotropes, we investigated the potential signal transduction pathway that conveys the inhibitory action of GnIH in GnRH neurons by using the GnRH neuronal cell line, GT1-7. We examined whether GnIH inhibits the action of kisspeptin and vasoactive intestinal polypeptide (VIP), positive regulators of GnRH neurons. Although GnIH significantly suppressed the stimulatory effect of kisspeptin on GnRH release in hypothalamic culture, GnIH had no inhibitory effect on kisspeptin stimulation of serum response element and nuclear factor of activated T-cell response element activities and ERK phosphorylation, indicating that GnIH may not directly inhibit kisspeptin signaling in GnRH neurons. On the contrary, GnIH effectively eliminated the stimulatory effect of VIP on p38 and ERK phosphorylation, c-Fos mRNA expression, and GnRH release. The use of pharmacological modulators strongly demonstrated the specific inhibitory action of GnIH on the adenylate cyclase/cAMP/protein kinase A pathway, suggesting a common inhibitory mechanism of GnIH action in GnRH neurons and gonadotropes.

    Original languageEnglish
    Pages (from-to)2198-2210
    Number of pages13
    JournalFASEB Journal
    Volume30
    Issue number6
    DOIs
    Publication statusPublished - 2016 Jun 1

    Keywords

    • GnIH receptor signaling
    • GPCR
    • RFamide-related peptide

    ASJC Scopus subject areas

    • Biochemistry
    • Biotechnology
    • Genetics
    • Molecular Biology

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