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Molecular Endocrinology, doi:10.1210/me.2005-0199
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Molecular Endocrinology 20 (5): 1090-1103
Copyright © 2006 by The Endocrine Society

Switching of NR5A Proteins Associated with the Inhibin {alpha}-Subunit Gene Promoter after Activation of the Gene in Granulosa Cells

Jennifer Weck and Kelly E. Mayo

Department of Biochemistry, Molecular Biology, and Cell Biology, and Center for Reproductive Science, Northwestern University, Evanston, Illinois 60208

Address all correspondence and requests for reprints to: Kelly E. Mayo, Department of Biochemistry, Molecular Biology, and Cell Biology, 2205 Tech Drive, Northwestern University, Evanston, Illinois 60208. E-mail: k-mayo{at}northwestern.edu.

The inhibin {alpha}-subunit gene is transcriptionally activated by FSH in ovarian granulosa cells during follicular growth. We have investigated the roles of the NR5A family nuclear receptors steroidogenic factor 1 (SF-1) and liver receptor homolog 1 (LRH-1) in transcriptional activation of the inhibin {alpha}-subunit gene. Transfection assays using an inhibin {alpha}-subunit promoter reporter in GRMO2 granulosa cells show that LRH-1 and SF-1 act similarly to increase promoter activity, and that the activity of both transcription factors is augmented by the coactivators cAMP response element-binding protein-binding protein and steroid receptor coactivator 1. However, chromatin immunoprecipitation experiments illustrate differential dynamic association of LRH-1 and SF-1 with the {alpha}-subunit inhibin promoter in both primary cells and the GRMO2 granulosa cell line such that hormonal stimulation of transcription results in an apparent replacement of SF-1 with LRH-1. Transcriptional stimulation of the inhibin {alpha}-subunit gene is dependent on MAPK kinase activity, as is the dynamic association/disassociation of SF-1 and LRH-1 with the promoter. Inhibition of the phosphatidylinositol 3-kinase signaling pathway influences promoter occupancy and transcriptional activation by SF-1 but not LRH-1, suggesting a possible mechanistic basis for the distinct functions of these NR5A proteins in inhibin {alpha}-subunit gene regulation.

NURSA Molecule Pages Link:

Nuclear Receptors:   SF-1  |  LRH-1
Coregulators:   CBP  |  SRC-1



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