Stimulation of the preprothyrotropin-releasing hormone gene by epidermal growth factor

Endocrinology
Y RenM Mori

Abstract

Regulation of the expression of the prepro-TRH (ppTRH) gene by epidermal growth factor (EGF) was investigated. The i.p. injection of EGF significantly stimulated hypothalamic ppTRH messenger RNA levels in rats. To clarify whether this stimulatory effect of EGF could be exerted at the level of gene transcription, the 5'-flanking region (-1893/+127) of the mouse ppTRH gene fused to a luciferase reporter gene was transiently transfected into pituitary GH4C1 cells, and the effect of EGF on gene transcription was measured by a luciferase assay. EGF stimulated ppTRH gene promoter activity in a time- and dose-dependent manner. Deletion analysis revealed that two different regions of the promoter, between -254 and -218 [EGF response element-1 (EGFRE1)] and between -130 and -84 (EGFRE2) were required for full stimulation by EGF. The two EGFREs possessed putative binding sequences for the transcription factor Sp1, and they functioned cooperatively in heterologous promoters. Nuclear extracts from GH4C1 cells specifically bound those two EGFREs in gel retardation assays. Two protein-DNA complexes were found on EGFRE1, whereas four complexes were observed on EGFRE2. Although the binding of nuclear extracts to EGFRE1 was competed for by the ...Continue Reading

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Citations

Sep 24, 2008·The Journal of Biological Chemistry·Matthias D KaeserBeverly M Emerson
Jan 29, 2011·American Journal of Physiology. Gastrointestinal and Liver Physiology·Ravinder K GillSeema Saksena
Jun 26, 2001·Journal of Cellular Physiology·A R BlackJ Azizkhan-Clifford
Sep 25, 2012·Molecular and Cellular Endocrinology·Franck ChiappiniAnthony N Hollenberg
Jan 27, 2011·Biochimica Et Biophysica Acta·Antonieta Cote-VélezPatricia Joseph-Bravo
Nov 28, 2008·Molecular Endocrinology·Shunichi MatsumotoMasatomo Mori
Jul 14, 2007·Endocrinology·Koshi HashimotoMasatomo Mori
Jan 17, 2003·American Journal of Physiology. Cell Physiology·Hua XuFayez K Ghishan
Feb 15, 2001·American Journal of Physiology. Cell Physiology·H XuF K Ghishan
Jul 10, 2001·American Journal of Physiology. Cell Physiology·H XuF K Ghishan

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