Molecular basis for the activation of gonadotropin-inhibitory hormone gene transcription by corticosterone

You Lee Son, Takayoshi Ubuka, Misato Narihiro, Yujiro Fukuda, Itaru Hasunuma, Kazutoshi Yamamoto, Denise D. Belsham, Kazuyoshi Tsutsui*

*この研究の対応する著者

    研究成果: Article査読

    72 被引用数 (Scopus)

    抄録

    The inhibitory effect of stress on reproductive function is potentially mediated by high concentrations of circulating glucocorticoids (GCs) acting via the GC receptor (GR). Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that inhibits gonadotropin secretion. GnIH may mediate stress-induced reproductive dysfunction. However, it is not yet known whether GCbound GR is directly involved in GnIH transcription. Here, we demonstrated the localization of GR mRNA in GnIH neurons in the paraventricular nucleus of quail, suggesting that GC can directly regulate GnIH transcription. We next showed that 24 hours of treatment with corticosterone (CORT) increase GnIH mRNA expression in the quail diencephalon. We further investigated the mechanism of activation of GnIH transcription by CORT using a GnIH-expressing neuronal cell line, rHypoE-23, derived from rat hypothalamus. We found the expression of GR mRNA in rHypoE-23 cells and increased GnIHmRNAexpression by 24 hours of CORT treatment.Wefinally characterized the promoter activity of rat GnIH gene stimulated by CORT. Through DNA deletion analysis, we identified a CORT-responsive region at 2000-1501 bp upstream of GnIH precursor coding region. This region included 2 GC response elements (GREs) at -1665 and -1530 bp. Mutation of -1530 GRE abolished CORT responsiveness. We also found CORT-stimulated GR recruitment at the GnIH promoter region containing the -1530 GRE. These results provide a putative molecular basis for transcriptional activation of GnIH under stress by demonstrating that CORT directly induces GnIH transcription by recruitment of GR to its promoter.

    本文言語English
    ページ(範囲)1817-1826
    ページ数10
    ジャーナルEndocrinology
    155
    5
    DOI
    出版ステータスPublished - 2014

    ASJC Scopus subject areas

    • 内分泌学

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