This Article Full Text Full Text (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 Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by El-Hefnawy, T. Articles by Zeleznik, A. J. Search for Related Content PubMed PubMed Citation Articles by El-Hefnawy, T. Articles by Zeleznik, A. J. Pubmed/NCBI databases Substance via MeSH Hazardous Substances DB MENOTROPINS

Synergism Between FSH and Activin in the Regulation of Proliferating Cell Nuclear Antigen (PCNA) and Cyclin D2 Expression in Rat Granulosa Cells

Department of Physiology and Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261

Address all correspondence and requests for reprints to: Anthony J. Zeleznik, Ph.D., 830 Scaife Hall, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, Pennsylvania 15261. E-mail: zeleznik+{at}pitt.edu

Follicular development is associated with both proliferation and differentiation of granulosa cells under the control of FSH. We show that regulation of genes involved in cellular proliferation by FSH can be functionally separated from the regulation of genes involved in granulosa cell differentiation by synergistic actions of activin and T. Incubation of undifferentiated rat granulosa cells with FSH, forskolin, activin-A, or T alone did not influence either the expression of the proliferation-associated genes cyclin D2 and proliferating cell nuclear antigen or the differentiation-associated genes P450 aromatase, LH receptor, P450 cholesterol side-chain cleavage enzyme, and 3ß-hydroxysteroid dehydrogenase. However, when granulosa cells were stimulated with either FSH or forskolin in the presence of activin-A, significant increases (P < 0.05) were observed for cyclin D2 and proliferating cell nuclear antigen at both the mRNA and protein levels as well as mRNAs for P450 aromatase, LH receptor, P450 cholesterol side-chain cleavage enzyme and 3ß-hydroxysteroid dehydrogenase. Although T synergized with FSH to increase the expression of mRNAs for P450 aromatase, LH receptor, P450 cholesterol side-chain cleavage enzyme, and 3ß-hydroxysteroid dehydrogenase, it did not interact with FSH to increase the expression of mRNAs for cyclin D2 and proliferating cell nuclear antigen. The differences in the actions of activin and T could provide a cellular mechanism by which FSH-regulated granulosa cell proliferation could be functionally separated from FSH-regulated granulosa cell differentiation.

This article has been cited by other articles:

				S. A. Pangas, C. J. Jorgez, M. Tran, J. Agno, X. Li, C. W. Brown, T. R. Kumar, and M. M. Matzuk Intraovarian Activins Are Required for Female Fertility Mol. Endocrinol., October 1, 2007; 21(10): 2458 - 2471. [Abstract] [Full Text] [PDF]

				B. D. Looyenga and G. D. Hammer Genetic Removal of Smad3 from Inhibin-Null Mice Attenuates Tumor Progression by Uncoupling Extracellular Mitogenic Signals from the Cell Cycle Machinery Mol. Endocrinol., October 1, 2007; 21(10): 2440 - 2457. [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]

				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]

				P. P. Kayampilly and K. M. J. Menon Dihydrotestosterone Inhibits Insulin-Stimulated Cyclin D2 Messenger Ribonucleic Acid Expression in Rat Ovarian Granulosa Cells by Reducing the Phosphorylation of Insulin Receptor Substrate-1 Endocrinology, January 1, 2006; 147(1): 464 - 471. [Abstract] [Full Text] [PDF]

				A. Pierre, C. Pisselet, J. Dupont, M. Bontoux, and P. Monget Bone Morphogenetic Protein 5 Expression in the Rat Ovary: Biological Effects on Granulosa Cell Proliferation and Steroidogenesis Biol Reprod, December 1, 2005; 73(6): 1102 - 1108. [Abstract] [Full Text] [PDF]

				Y. Park, E. T. Maizels, Z. J. Feiger, H. Alam, C. A. Peters, T. K. Woodruff, T. G. Unterman, E. J. Lee, J. L. Jameson, and M. Hunzicker-Dunn Induction of Cyclin D2 in Rat Granulosa Cells Requires FSH-dependent Relief from FOXO1 Repression Coupled with Positive Signals from Smad J. Biol. Chem., March 11, 2005; 280(10): 9135 - 9148. [Abstract] [Full Text] [PDF]

				L M McClusky Stage and season effects on cell cycle and apoptotic activities of germ cells and Sertoli cells during spermatogenesis in the spiny dogfish (Squalus acanthias) Reproduction, January 1, 2005; 129(1): 89 - 102. [Abstract] [Full Text] [PDF]

				A.L. Johnson, J.T. Bridgham, and D.C. Woods Cellular Mechanisms and Modulation of Activin A- and Transforming Growth Factor {beta}-Mediated Differentiation in Cultured Hen Granulosa Cells Biol Reprod, December 1, 2004; 71(6): 1844 - 1851. [Abstract] [Full Text] [PDF]

				M. K. Schuster, B. Schmierer, A. Shkumatava, and K. Kuchler Activin A and Follicle-Stimulating Hormone Control Tight Junctions in Avian Granulosa Cells by Regulating Occludin Expression Biol Reprod, May 1, 2004; 70(5): 1493 - 1499. [Abstract] [Full Text] [PDF]

				P. P. Kayampilly and K. M. J. Menon Inhibition of Extracellular Signal-Regulated Protein Kinase-2 Phosphorylation by Dihydrotestosterone Reduces Follicle-Stimulating Hormone-Mediated Cyclin D2 Messenger Ribonucleic Acid Expression in Rat Granulosa Cells Endocrinology, April 1, 2004; 145(4): 1786 - 1793. [Abstract] [Full Text] [PDF]

				A. J. Zeleznik, L. Little-Ihrig, and S. Ramasawamy Administration of Dihydrotestosterone to Rhesus Monkeys Inhibits Gonadotropin-Stimulated Ovarian Steroidogenesis J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 860 - 866. [Abstract] [Full Text] [PDF]

				A. J. Zeleznik, D. Saxena, and L. Little-Ihrig Protein Kinase B Is Obligatory for Follicle-Stimulating Hormone-Induced Granulosa Cell Differentiation Endocrinology, September 1, 2003; 144(9): 3985 - 3994. [Abstract] [Full Text] [PDF]

				B. Schmierer, M. K. Schuster, A. Shkumatava, and K. Kuchler Activin A Signaling Induces Smad2, but Not Smad3, Requiring Protein Kinase A Activity in Granulosa Cells from the Avian Ovary J. Biol. Chem., May 30, 2003; 278(23): 21197 - 21203. [Abstract] [Full Text] [PDF]

				J. J. Buzzard, P. G. Farnworth, D. M. de Kretser, A. E. O'Connor, N. G. Wreford, and J. R. Morrison Proliferative Phase Sertoli Cells Display a Developmentally Regulated Response to Activin in Vitro Endocrinology, February 1, 2003; 144(2): 474 - 483. [Abstract] [Full Text] [PDF]

				Y. Wang and W. Ge Involvement of Cyclic Adenosine 3',5'-Monophosphate in the Differential Regulation of Activin {beta}A and {beta}B Expression by Gonadotropin in the Zebrafish Ovarian Follicle Cells Endocrinology, February 1, 2003; 144(2): 491 - 499. [Abstract] [Full Text] [PDF]

				B. Schmierer, M. K. Schuster, A. Shkumatava, and K. Kuchler Activin and Follicle-Stimulating Hormone Signaling Are Required for Long-Term Culture of Functionally Differentiated Primary Granulosa Cells from the Chicken Ovary Biol Reprod, February 1, 2003; 68(2): 620 - 627. [Abstract] [Full Text] [PDF]

				C. Welt, Y. Sidis, H. Keutmann, and A. Schneyer Activins, Inhibins, and Follistatins: From Endocrinology to Signaling. A Paradigm for the New Millennium Experimental Biology and Medicine, October 1, 2002; 227(9): 724 - 752. [Abstract] [Full Text] [PDF]

				P. K. Pradeep, X. Li, H. Peegel, and K. M. J. Menon Dihydrotestosterone Inhibits Granulosa Cell Proliferation by Decreasing the Cyclin D2 mRNA Expression and Cell Cycle Arrest at G1 Phase Endocrinology, August 1, 2002; 143(8): 2930 - 2935. [Abstract] [Full Text] [PDF]