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

    Research output: Contribution to journalArticle

    51 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)1817-1826
    Number of pages10
    JournalEndocrinology
    Volume155
    Issue number5
    DOIs
    Publication statusPublished - 2014

      Fingerprint

    ASJC Scopus subject areas

    • Endocrinology

    Cite this

    Son, Y. L., Ubuka, T., Narihiro, M., Fukuda, Y., Hasunuma, I., Yamamoto, K., Belsham, D. D., & Tsutsui, K. (2014). Molecular basis for the activation of gonadotropin-inhibitory hormone gene transcription by corticosterone. Endocrinology, 155(5), 1817-1826. https://doi.org/10.1210/en.2013-2076