Journal article
GnRH Regulates Early Growth Response Protein 1 Transcription Through Multiple Promoter Elements
Molecular endocrinology (Baltimore, Md.), Vol.16(2), pp.221-233
02/01/2002
Handle:
https://hdl.handle.net/2376/108645
PMID: 11818496
Abstract
Abstract
Pulsatile secretion of GnRH is the major regulator of gonadotropin (LH, FSH) gene expression and secretion. Recently, GnRH has been shown to rapidly stimulate the expression of early growth response protein-1 (Egr-1), a transcription factor that is essential for LHβ gene expression in the pituitary. In this study, we examined the regulatory elements and signal transduction pathways by which GnRH regulates Egr-1 transcription. Deletion analysis of the murine Egr-1 promoter identified two regions (−370 to −342 and −116 to −73) that are critical for GnRH responsiveness in αT3 pituitary gonadotrope cells. The first region, which contains two serum response elements (SREs), contributed about 70-80% of GnRH inducibility, whereas the second region, which contains two SREs and one Ets binding site, conferred an additional 20-30% of activity. Mutations that abolish protein binding to these SREs and Ets binding sites completely eliminated GnRH-mediated transcriptional activation of the Egr-1 promoter. Mutation of cAMP response element reduced promoter activity by 40%. Using specific protein kinase inhibitors, GnRH stimulation of Egr-1 expression was found to be dependent on PKC/ERK pathways. In addition, GnRH activated p90 ribosomal S6 kinase, which has the potential to phosphorylate serum response factor and cAMP response element binding protein. We conclude that GnRH stimulation of Egr-1 gene expression requires several distinct SREs/Ets elements and a cAMP response element and is mediated via activation of PKC/ERK signaling pathways.
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Details
- Title
- GnRH Regulates Early Growth Response Protein 1 Transcription Through Multiple Promoter Elements
- Creators
- W. Rachel Duan - 1Division of Endocrinology, Metabolism, and Molecular Medicine (W.R.D., M.I., Y.P., J.L.J.), Chicago, Illinois 60611Masafumi Ito - 1Division of Endocrinology, Metabolism, and Molecular Medicine (W.R.D., M.I., Y.P., J.L.J.), Chicago, Illinois 60611Youngkyu Park - 1Division of Endocrinology, Metabolism, and Molecular Medicine (W.R.D., M.I., Y.P., J.L.J.), Chicago, Illinois 60611Evelyn T Maizels - 2Cell and Molecular Biology (E.T.M., M.H.D.), Northwestern University Medical School, Chicago, Illinois 60611Mary Hunzicker-Dunn - 2Cell and Molecular Biology (E.T.M., M.H.D.), Northwestern University Medical School, Chicago, Illinois 60611J. Larry Jameson - 1Division of Endocrinology, Metabolism, and Molecular Medicine (W.R.D., M.I., Y.P., J.L.J.), Chicago, Illinois 60611
- Publication Details
- Molecular endocrinology (Baltimore, Md.), Vol.16(2), pp.221-233
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- Oxford University Press
- Identifiers
- 99900547801701842
- Language
- English
- Resource Type
- Journal article