A composite hormone response element regulates transcription of the rat GHRH receptor gene

Haruo Nogami, Yoshiki Hiraoka, Maki Matsubara, Eriko Nonobe, Toshio Harigaya, Masateru Katayama, Noriaki Hemmi, Shuzo Kobayashi, Koichi Mogi, Sadakazu Aiso, Koki Kawamura, Setsuji Hisano

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

To further elucidate the molecular mechanisms underlying the transcriptional regulation of the GHRH receptor (GHRH-R) gene, hormonal regulation of the promoter activity of this gene was examined. An approximately 3-kb genomic fragment spanning the promoter region of the gene was sequenced and the transcription start site was determined by RT-PCR and RNase protection assay. A major start site was localized at -105 (relative to the translation initiation codon, ATG), and a pit-1 binding sequence characteristic of pituitary specific genes was found at -155 to -146. Deletion and mutation studies demonstrated this site to be functional. In the presence of dexamethasone, the GHRH-R promoter (from -2935 to -11) directed luciferase expression in MtT-S cells, a somatotropic cell line, but not in the PC12 cells that normally do not express GHRH-R. While T3, all trans-RA, and 9cis-RA alone weakly enhanced the reporter gene expression, each of these substances was found to act as a synergistic enhancer in the presence of dexamethasone. Additional deletion and mutation analyses demonstrated a functional RA response element at -1090 to -1074. Two functional glucocorticoid response elements and a T3 response element were found in an 80-bp 5′-flanking sequence of the pit-1 site. Interestingly, it is suggested that the 6-bp half-site AGGACA (from -209 to -204) functions as a 3′-half-site of T3 response element as well as a 5′-half-site of one of the glucocorticoid response elements.

Original languageEnglish
Pages (from-to)1318-1326
Number of pages9
JournalEndocrinology
Volume143
Issue number4
DOIs
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Endocrinology

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