Endocrinology, Vol 137, 3437-3446, Copyright © 1996 by Endocrine Society

ARTICLES

Transcriptional repression of the ovine follicle-stimulating hormone- beta gene by 17 beta-estradiol

CD Miller and WL Miller
Department of Biochemistry, North Carolina State University, Raleigh 27695-7622, USA.

Direct transcriptional inhibition of the gene that encodes ovine FSH beta-subunit (oFSH beta) by 17 beta-estradiol (E2) has been previously demonstrated by our laboratory. To determine which cis-acting elements in the 5'-flanking region of this gene may be involved in E2 regulation, DNA constructs containing deletions of the 5'-end of the oFSH beta gene were fused to a luciferase reporter and tested in transient transfection assays. These oFSH beta-luciferase constructs and the human E2 receptor expression vector (HEO) were transfected into primary cultures of ovine pituitary cells and subsequently tested with E2. Expression of the largest oFSH beta-luciferase construct (-4741 to +759 of oFSH beta) was inhibited 50% by 20 nM E2. Repression was dependent upon cotransfection of estrogen receptor (HEO) and was E2 dose dependent, with an apparent ED50 similar to that of the positive control consensus estrogen-responsive element construct, ERETk-LUC (ED50 = 50 pM). Deletion studies indicated that sequences between- 105 and -84 bp are necessary for this repression. In addition, a synthetic nucleotide containing oFSH beta sequences from - 105 to -72 could direct E2-dependent repression of a heterologous thymidine kinase promoter that drives luciferase expression. Additional experiments showed that no tissue-specific elements were required for either basal expression or E2-directed transcriptional repression. Although there are no consensus DNA response elements for the estrogen receptor between -105 and +759 of the oFSH beta gene, cotransfection of a mutant E2 receptor lacking the DNA-binding domain (HE-11) failed to mediate E2- dependent inhibition. Gel retardation studies, using the oligonucleotide-containing oFSH beta sequences from -105 to -72, indicated no evidence of direct binding of the estrogen receptor to DNA from -105 to -72. The studies presented here indicate that transcriptional repression of the oFSH beta gene by E2 may be directed in vivo by 5'-flanking sequences between -105 and -72 of the oFSH beta gene. Furthermore, the data suggest that inhibition is mediated via E2 receptor-protein interactions with basal transcription factors that may bind to the -105/-72 DNA directly.

This article has been cited by other articles:

				C. Glidewell-Kenney, J. Weiss, L. A. Hurley, J. E. Levine, and J. L. Jameson Estrogen Receptor {alpha} Signaling Pathways Differentially Regulate Gonadotropin Subunit Gene Expression and Serum Follicle-Stimulating Hormone in the Female Mouse Endocrinology, August 1, 2008; 149(8): 4168 - 4176. [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]

				M. A. McDevitt, C. Glidewell-Kenney, J. Weiss, P. Chambon, J. L. Jameson, and J. E. Levine Estrogen Response Element-Independent Estrogen Receptor (ER)-{alpha} Signaling Does Not Rescue Sexual Behavior but Restores Normal Testosterone Secretion in Male ER{alpha} Knockout Mice Endocrinology, November 1, 2007; 148(11): 5288 - 5294. [Abstract] [Full Text] [PDF]

				L. L. Burger, D. J. Haisenleder, G. M. Wotton, K. W. Aylor, A. C. Dalkin, and J. C. Marshall The regulation of FSHbeta transcription by gonadal steroids: testosterone and estradiol modulation of the activin intracellular signaling pathway Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E277 - E285. [Abstract] [Full Text] [PDF]

				J. Lindzey, F. L Jayes, M. M Yates, J. F Couse, and K. S Korach The bi-modal effects of estradiol on gonadotropin synthesis and secretion in female mice are dependent on estrogen receptor-{alpha}. J. Endocrinol., October 1, 2006; 191(1): 309 - 317. [Abstract] [Full Text] [PDF]

				P. Su, J. C. Wu, J. R. Sommer, A. J. Gore, R. M. Petters, and W. L. Miller Conditional Induction of Ovulation in Mice Biol Reprod, October 1, 2005; 73(4): 681 - 687. [Abstract] [Full Text] [PDF]

				M-O Faure, L Nicol, S Fabre, J Fontaine, N Mohoric, A McNeilly, and C Taragnat BMP-4 inhibits follicle-stimulating hormone secretion in ewe pituitary J. Endocrinol., July 1, 2005; 186(1): 109 - 121. [Abstract] [Full Text] [PDF]

				L L Burger, D J Haisenleder, A C Dalkin, and J C Marshall Regulation of gonadotropin subunit gene transcription J. Mol. Endocrinol., December 1, 2004; 33(3): 559 - 584. [Abstract] [Full Text] [PDF]

				B. E. West, G. E. Parker, J. J. Savage, P. Kiratipranon, K. S. Toomey, L. R. Beach, S. C. Colvin, K. W. Sloop, and S. J. Rhodes Regulation of the Follicle-Stimulating Hormone {beta} Gene by the LHX3 LIM-Homeodomain Transcription Factor Endocrinology, November 1, 2004; 145(11): 4866 - 4879. [Abstract] [Full Text] [PDF]

				C. K. Cheng, B. K. C. Chow, and P. C. K. Leung An Activator Protein 1-Like Motif Mediates 17{beta}-Estradiol Repression of Gonadotropin-Releasing Hormone Receptor Promoter via an Estrogen Receptor {alpha}-Dependent Mechanism in Ovarian and Breast Cancer Cells Mol. Endocrinol., December 1, 2003; 17(12): 2613 - 2629. [Abstract] [Full Text] [PDF]

				M. Jakacka, M. Ito, F. Martinson, T. Ishikawa, E. J. Lee, and J. L. Jameson An Estrogen Receptor (ER){alpha} Deoxyribonucleic Acid-Binding Domain Knock-In Mutation Provides Evidence for Nonclassical ER Pathway Signaling in Vivo Mol. Endocrinol., October 1, 2002; 16(10): 2188 - 2201. [Abstract] [Full Text] [PDF]

				M. M. Zakaria, K.-H. Jeong, C. Lacza, and U. B. Kaiser Pituitary Homeobox 1 Activates the Rat FSH{beta} (rFSH{beta}) Gene through Both Direct and Indirect Interactions with the rFSH{beta} Gene Promoter Mol. Endocrinol., August 1, 2002; 16(8): 1840 - 1852. [Abstract] [Full Text] [PDF]

				J. M. Kuhn, H. Lefebvre, C. Duparc, A. Pellerin, J. P. Luton, and G. Strauch Cosecretion of Estrogen and Inhibin B by a Feminizing Adrenocortical Adenoma: Impact on Gonadotropin Secretion J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2367 - 2375. [Abstract] [Full Text] [PDF]

				V. V. Vasilyev, F. Pernasetti, S. B. Rosenberg, M. J. Barsoum, D. A. Austin, N. J. G. Webster, and P. L. Mellon Transcriptional Activation of the Ovine Follicle-Stimulating Hormone-{beta} Gene by Gonadotropin- Releasing Hormone Involves Multiple Signal Transduction Pathways Endocrinology, May 1, 2002; 143(5): 1651 - 1659. [Abstract] [Full Text] [PDF]

				J. Pfeilschifter, R. Koditz, M. Pfohl, and H. Schatz Changes in Proinflammatory Cytokine Activity after Menopause Endocr. Rev., February 1, 2002; 23(1): 90 - 119. [Abstract] [Full Text] [PDF]

				H.-J. Huang, J. Sebastian, B. D. Strahl, J. C. Wu, and W. L. Miller The Promoter for the Ovine Follicle-Stimulating Hormone-{beta} Gene (FSH{beta}) Confers FSH{beta}-Like Expression on Luciferase in Transgenic Mice: Regulatory Studies in Vivo and in Vitro Endocrinology, June 1, 2001; 142(6): 2260 - 2266. [Abstract] [Full Text] [PDF]

				H.-J. Huang, J. Sebastian, B. D. Strahl, J. C. Wu, and W. L. Miller Transcriptional Regulation of the Ovine Follicle-Stimulating Hormone-{beta} Gene by Activin and Gonadotropin-Releasing Hormone (GnRH): Involvement of Two Proximal Activator Protein-1 Sites for GnRH Stimulation Endocrinology, June 1, 2001; 142(6): 2267 - 2274. [Abstract] [Full Text] [PDF]

				M. Baratta, L.A. West, A.M. Turzillo, and T.M. Nett Activin Modulates Differential Effects of Estradiol on Synthesis and Secretion of Follicle-Stimulating Hormone in Ovine Pituitary Cells Biol Reprod, February 1, 2001; 64(2): 714 - 719. [Abstract] [Full Text]

				D. G. Monroe, D. F. Jin, and M. M. Sanders Estrogen Opposes the Apoptotic Effects of Bone Morphogenetic Protein 7 on Tissue Remodeling Mol. Cell. Biol., July 1, 2000; 20(13): 4626 - 4634. [Abstract] [Full Text]

				T. W. Abel, M. L. Voytko, and N. E. Rance The Effects of Hormone Replacement Therapy on Hypothalamic Neuropeptide Gene Expression in a Primate Model of Menopause J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2111 - 2118. [Abstract] [Full Text]

				B. D. Strahl, H.-J. Huang, J. Sebastian, B. R. Ghosh, and W. L. Miller Transcriptional Activation of the Ovine Follicle-Stimulating Hormone {beta}-Subunit Gene by Gonadotropin-Releasing Hormone: Involvement of Two Activating Protein-1-Binding Sites and Protein Kinase C Endocrinology, November 1, 1998; 139(11): 4455 - 4465. [Abstract] [Full Text] [PDF]

				B. D. Strahl, H.-J. Huang, N. R. Pedersen, J. C. Wu, B. R. Ghosh, and W. L. Miller Two Proximal Activating Protein-1-Binding Sites Are Sufficient to Stimulate Transcription of the Ovine Follicle-Stimulating Hormone-{beta} Gene Endocrinology, June 1, 1997; 138(6): 2621 - 2631. [Abstract] [Full Text] [PDF]

				M. Jakacka, M. Ito, J. Weiss, P.-Y. Chien, B. D. Gehm, and J. L. Jameson Estrogen Receptor Binding to DNA Is Not Required for Its Activity through the Nonclassical AP1 Pathway J. Biol. Chem., April 20, 2001; 276(17): 13615 - 13621. [Abstract] [Full Text] [PDF]