Evidence for autocrine inhibition of gonadotropin-releasing hormone (GnRH) gene transcription by GnRH in hypothalamic GT1-1 neuronal cells

Sehyung Cho, Jin Han, Woong Sun, Donchan Choi, Hyuk Bang Kwon, Hubertus Jarry, Wolfgang Wuttke, Kyungjin Kim

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

To examine whether an ultrashort feedback mechanism of gonadotropin-releasing hormone (GnRH) operates at the level of gene transcription, we studied the effects of GnRH analogs on GnRH promoter activity and GnRH mRNA level in hypothalamic GT1-1 neuronal cells. Treatment of GT1-1 cells with buserelin, a GnRH agonist, or native GnRH for 24 h significantly decreased GnRH promoter activity and its mRNA level, whereas that with GnRH antagonists, antide or [D-Phe2,D-Ala6]-GnRH, showed no effect. The inhibitory effects of buserelin on GnRH gene transcription and GnRH mRNA level were dose-related, and a significant inhibition was observed in cells treated with buserelin at concentrations higher than 0.1 μM. Time-course experiments showed that significant decreases in GnRH promoter-driven luciferase activity and GnRH mRNA level were observed within 12 h and sustained up to 48 h. Moreover, treatment with GnRH agonist for 12 h significantly decreased the transcription rate of the mouse GnRH gene, as revealed by nuclear run-on transcription assay. The promoter analysis with the 5'-deletional constructs demonstrated that cis-acting elements important for GnRH autoregulation by GnRH agonist reside within -854 bp upstream from the transcription start site. These data clearly demonstrate that GnRH can exert autocrine regulation at the level of GnRH gene transcription.

Original languageEnglish
Pages (from-to)51-58
Number of pages8
JournalMolecular Brain Research
Volume50
Issue number1-2
DOIs
Publication statusPublished - 1997 Oct 15

Keywords

  • Autocrine regulation
  • GT1-1 cell
  • Gonadotropin-releasing hormone
  • Transcriptional regulation

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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