This Article Full Text Full Text (PDF) All Versions of this Article: 20/5/1090    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weck, J. Articles by Mayo, K. E. Search for Related Content PubMed PubMed Citation Articles by Weck, J. Articles by Mayo, K. E.

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

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 -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 -subunit gene. Transfection assays using an inhibin -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 -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 -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 -subunit gene regulation.

NURSA Molecule Pages Link:

Nuclear Receptors:   SF-1  |  LRH-1

Coregulators:   CBP  |  SRC-1

This article has been cited by other articles:

				A. E. Lewis, M. Rusten, E. A. Hoivik, E. L. Vikse, M. L. Hansson, A. E. Wallberg, and M. Bakke Phosphorylation of Steroidogenic Factor 1 Is Mediated by Cyclin-Dependent Kinase 7 Mol. Endocrinol., January 1, 2008; 22(1): 91 - 104. [Abstract] [Full Text] [PDF]

				M. Doghman, T. Karpova, G. A. Rodrigues, M. Arhatte, J. De Moura, L. R. Cavalli, V. Virolle, P. Barbry, G. P. Zambetti, B. C. Figueiredo, et al. Increased Steroidogenic Factor-1 Dosage Triggers Adrenocortical Cell Proliferation and Cancer Mol. Endocrinol., December 1, 2007; 21(12): 2968 - 2987. [Abstract] [Full Text] [PDF]

				H. A Ferris, H. E Walsh, J. Stevens, P. C Fallest, and M. A Shupnik Luteinizing Hormone Beta Promoter Stimulation by Adenylyl Cyclase and Cooperation with Gonadotropin-Releasing Hormone 1 in Transgenic Mice and LBetaT2 Cells Biol Reprod, December 1, 2007; 77(6): 1073 - 1080. [Abstract] [Full Text] [PDF]

				L. Lin, P. Philibert, B. Ferraz-de-Souza, D. Kelberman, T. Homfray, A. Albanese, V. Molini, N. J. Sebire, S. Einaudi, G. S. Conway, et al. Heterozygous Missense Mutations in Steroidogenic Factor 1 (SF1/Ad4BP, NR5A1) Are Associated with 46,XY Disorders of Sex Development with Normal Adrenal Function J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 991 - 999. [Abstract] [Full Text] [PDF]

				J. Guo, S.-X. Tao, M. Chen, Y.-Q. Shi, Z.-Q. Zhang, Y.-C. Li, X.-S. Zhang, Z.-Y. Hu, and Y.-X. Liu Heat Treatment Induces Liver Receptor Homolog-1 Expression in Monkey and Rat Sertoli Cells Endocrinology, March 1, 2007; 148(3): 1255 - 1265. [Abstract] [Full Text] [PDF]

				W. Zheng, J. Yang, Q. Jiang, Z. He, and L. M Halvorson Liver receptor homologue-1 regulates gonadotrope function J. Mol. Endocrinol., February 1, 2007; 38(2): 207 - 219. [Abstract] [Full Text] [PDF]

				D. Saxena, R. Escamilla-Hernandez, L. Little-Ihrig, and A. J. Zeleznik Liver Receptor Homolog-1 and Steroidogenic Factor-1 Have Similar Actions on Rat Granulosa Cell Steroidogenesis Endocrinology, February 1, 2007; 148(2): 726 - 734. [Abstract] [Full Text] [PDF]

				G. Benoit, A. Cooney, V. Giguere, H. Ingraham, M. Lazar, G. Muscat, T. Perlmann, J.-P. Renaud, J. Schwabe, F. Sladek, et al. International Union of Pharmacology. LXVI. Orphan Nuclear Receptors Pharmacol. Rev., December 1, 2006; 58(4): 798 - 836. [Abstract] [Full Text] [PDF]

				T. N. Parakh, J. A. Hernandez, J. C. Grammer, J. Weck, M. Hunzicker-Dunn, A. J. Zeleznik, and J. H. Nilson Follicle-stimulating hormone/cAMP regulation of aromatase gene expression requires beta-catenin PNAS, August 15, 2006; 103(33): 12435 - 12440. [Abstract] [Full Text] [PDF]