Suppression of GnRH gene expression in GT1-1 hypothalamic neuronal cells: Action of protein kinase C

Woong Sun, Young S. Choe, Young J. Lee, Kyungjin Kim

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We attempted to elucidate molecular mechanisms of gonadotropin-releasing hormone (GnRH) gene regulation by the protein kinase C (PKC) pathway in GT1- 1 cells. Activation of PKC with 12-tetra-decanoylphorbol-13-acetate (TPA) or inhibition with staurosporine or calphostin C down-regulated GnRH mRNA levels. A serial deletion mutant analysis revealed that this suppression was mediated by the proximal region (-187/-69) of the mouse GnRH promoter. TPA transiently induced c-fos mRNA, whereas staurosporine or calphostin C failed to do so. However, PKC inhibitors blocked the TPA-evoked c-fos induction. Over-expression of PKCα down-regulated GnRH promoter activity, indicating that PKC activation was sufficient to inhibit GnRH gene expression. These results suggest that both activation and inhibition of PKC decrease the GnRH gene expression in the GT1-1 cells probably through different signal cascade mechanisms.

Original languageEnglish
Pages (from-to)3541-3546
Number of pages6
JournalNeuroreport
Volume8
Issue number16
DOIs
Publication statusPublished - 1997

Keywords

  • C-fos
  • Calphostin C
  • GT1-1
  • GnRH
  • Overexpression
  • Promoter
  • Protein kinase C
  • Staurosporine
  • TPA

ASJC Scopus subject areas

  • Neuroscience(all)

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