Molecular mechanisms for corticotropin-releasing hormone gene repression by glucocorticoid in BE(2)C neuronal cell line

Etsuko Yamamori, Yasumasa Iwasaki, Takafumi Taguchi, Mitsuru Nishiyama, Masanori Yoshida, Masato Asai, Yutaka Oiso, Keiichi Itoi, Machiko Kambayashi, Kozo Hashimoto

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

The molecular mechanisms for the suppression of corticotropin-releasing hormone (CRH) gene expression by glucocorticoid remain to be clarified albeit the well-known physiological role of the glucocorticoid-induced negative feedback regulation of the gene. In this study, we examined the effect of glucocorticoid on CRH gene transcription using the human BE(2)C neuronal cell line, which expresses the CRH gene and produces CRH peptide intrinsically. Dexamethasone, a specific ligand for the glucocorticoid receptor (GR), potently suppressed human CRH 5′-promoter activity. The effect was GR-dependent, and was completely antagonized by antiglucocorticoid RU38486. Treatment with neither sodium butyrate nor trichostatin A abolished the suppression, thus making the possible involvement of histone deacetylase (HDACs) unlikely. The suppression was not influenced by the deletion or mutation of the proposed negative glucocorticoid-response element (nGRE) but was completely eliminated by that of cAMP-response element. Finally, overexpression of protein kinase A catalytic subunit antagonized the glucocorticoid suppression, whereas overexpression of GR enhanced it. Taken together, our data suggest that: (1) glucocorticoid exerts its negative effect on CRH gene transcription in a GR-dependent manner, but the GR-mediated inhibition appears to be independent of the nGRE; (2) HDACs do not play a significant role in the glucocorticoid repression; (3) some of the inhibitory events may take place through transrepression of protein kinase A by GR.

Original languageEnglish
Pages (from-to)142-148
Number of pages7
JournalMolecular and Cellular Endocrinology
Volume264
Issue number1-2
DOIs
Publication statusPublished - 2007 Jan 29

Keywords

  • Corticotropin-releasing hormone
  • Glucocorticoid
  • Histone deacetylase
  • Hypothalamus
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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