This Article Full Text Full Text (PDF) 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 Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Curtin, D. Articles by Shupnik, M. A. Search for Related Content PubMed PubMed Citation Articles by Curtin, D. Articles by Shupnik, M. A.

Small Nuclear RING Finger Protein Stimulates the Rat Luteinizing Hormone-ß Promoter by Interacting with Sp1 and Steroidogenic Factor-1 and Protects from Androgen Suppression

Departments of Pharmacology (D.C.), Physiology (H.A.F.), and Internal Medicine (M.G., M.A.S.), University of Virginia, Charlottesville, Virginia 22908; and Institute of Biomedicine (M.H., O.A.J., J.J.P.) and Department of Clinical Chemistry (O.A.J.), University of Helsinki and Helsinki University Central Hospital, FIN-00014 Helsinki, Finland

Address all correspondence and requests for reprints to: Margaret A. Shupnik, Ph.D, Department of Internal Medicine/Endocrinology, PO Box 800578 Health Sciences Center, University of Virginia, Charlottesville, Virginia 22908. E-mail: mas3x{at}virginia.edu.

GnRH controls expression of the LH subunit genes, and LHß, with the LHß subunit regulated most dramatically. Two enhancer regions, distal and proximal, on the rat LHß gene promoter cooperate for full basal expression and GnRH stimulation. It has been hypothesized that the transcription factors binding to these regions, Sp1, Egr-1, and steroidogenic factor 1 (SF-1), may interact directly or indirectly via a coactivator. One such coactivator may be small nuclear RING finger protein (SNURF), which is expressed in pituitary tissue and the LßT2 gonadotrope cell line. In transfection experiments in LßT2 cells, SNURF stimulated basal expression of LHß and increased overall GnRH stimulation. SNURF specifically stimulated LHß, with no effect on the -subunit promoter. SNURF interacts with Sp1 and SF-1, but not Egr-1, in pull-down experiments. Point mutations or deletions of SNURF functional domains demonstrated that Sp1 and SF-1 interactions with SNURF are required for SNURF stimulatory effects on the LHß promoter. Endogenous SNURF is associated with the LHß promoter on native chromatin, suggesting that it plays a physiological role in LHß gene expression. SNURF also binds the androgen receptor, and SNURF overexpression overcomes androgen suppression of GnRH-stimulated LHß but not subunit promoter activity. SNURF mutations that disrupt Sp1 or SF-1 binding eliminate rescue by SNURF. We conclude that SNURF may mediate interactions between the distal and proximal GnRH response regions of the LHß promoter to stimulate transcription and can also protect the promoter from androgen suppression.

NURSA Molecule Pages Link:

Nuclear Receptors:   AR  |  SF-1

Coregulators:   SNURF  |  CBP  |  p300

Ligands:   Dihydrotestosterone

This article has been cited by other articles:

				H. E. Walsh and M. A. Shupnik Proteasome Regulation of Dynamic Transcription Factor Occupancy on the GnRH-Stimulated Luteinizing Hormone {beta}-Subunit Promoter Mol. Endocrinol., February 1, 2009; 23(2): 237 - 250. [Abstract] [Full Text] [PDF]

				J.-F. Mouillet, X. Yan, Q. Ou, L. Jin, L. J. Muglia, P. A. Crawford, and Y. Sadovsky DEAD-Box Protein-103 (DP103, Ddx20) Is Essential for Early Embryonic Development and Modulates Ovarian Morphology and Function Endocrinology, May 1, 2008; 149(5): 2168 - 2175. [Abstract] [Full Text] [PDF]

				M. H. Hong, H. Sun, C. H. Jin, M. Chapman, J. Hu, W. Chang, K. Burnett, J. Rosen, A. Negro-Vilar, and J. N. Miner Cell-Specific Activation of the Human Skeletal {alpha}-Actin by Androgens Endocrinology, March 1, 2008; 149(3): 1103 - 1112. [Abstract] [Full Text] [PDF]

				T. Kowase, H. E. Walsh, D. S. Darling, and M. A. Shupnik Estrogen Enhances Gonadotropin-Releasing Hormone-Stimulated Transcription of the Luteinizing Hormone Subunit Promoters via Altered Expression of Stimulatory and Suppressive Transcription Factors Endocrinology, December 1, 2007; 148(12): 6083 - 6091. [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]

				D. W. Waring and J. L. Turgeon Estradiol Inhibition of Voltage-Activated and Gonadotropin-Releasing Hormone-Induced Currents in Mouse Gonadotrophs Endocrinology, December 1, 2006; 147(12): 5798 - 5805. [Abstract] [Full Text] [PDF]

				H. A. Ferris and M. A. Shupnik Mechanisms for Pulsatile Regulation of the Gonadotropin Subunit Genes by GNRH1 Biol Reprod, June 1, 2006; 74(6): 993 - 998. [Abstract] [Full Text] [PDF]

				M. Luo, M. Koh, J. Feng, Q. Wu, and P. Melamed Cross Talk in Hormonally Regulated Gene Transcription through Induction of Estrogen Receptor Ubiquitylation Mol. Cell. Biol., August 15, 2005; 25(16): 7386 - 7398. [Abstract] [Full Text] [PDF]