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Department of Molecular and Cellular Biology, Baylor College of Medicine (T.N.A., I.J.G.R., J.S.R.), Houston, Texas 77030; and the Department of Molecular and Cell Biology, University of California (P.B., G.L.F.), Berkeley, California 94720
Address all correspondence and requests for reprints to: Dr. JoAnne S. Richards, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030. E-mail: joanner{at}bcm.tmc.edu
Expression of serum/glucocorticoid-inducible kinase (Sgk), one member of an inducible serine/threonine kinase family, is induced by FSH/cAMP in rat granulosa cells cultured in defined medium. The FSH-stimulated pattern of sgk expression is biphasic, and transcriptional activation of the sgk gene depends on an intact Sp1/Sp3 binding site within the proximal promoter. To determine whether sgk was expressed in a hormone-dependent and physiologically relevant manner in vivo, the cellular levels of sgk messenger RNA (mRNA) and protein as well as the subcellular localization of this kinase were analyzed in ovaries containing follicles and corpora lutea at specific stages of differentiation. To stimulate follicular development and luteinization, hypophysectomized (H) rats were treated with estradiol (E; HE) and FSH (FSH; HEF) followed by hCG (hCG; HEF/hCG). To analyze Sgk in functional corpora lutea, PRL was administered to HEF/hCG rats, or ovaries of pregnant rats were obtained on day 7, 15, or 22 of gestation. In situ hybridization indicated that sgk mRNA was low/undetectable in granulosa cells of H and HE rats. An acute injection (iv) of FSH to HE rats rapidly increased sgk mRNA at 2 and 8 h. Sgk mRNA was also elevated in granulosa cells of preovulatory follicles of HEF rats and in luteal cells of HEF/hCG and pregnant rats. Northern blots and Western blots confirmed the in situ hybridization data, indicating that the amount and cellular localization Sgk protein were related to that of sgk mRNA. When the subcellular localization of this kinase was analyzed by immunohistochemistry, Sgk protein was nuclear in granulosa cells and some thecal cells of large preovulatory follicles. In contrast, Sgk protein was cytoplasmic in luteal cells as well as some cells within the stromal compartment. Intense immunostaining was also observed in oocytes present in primordial follicles, but not in growing follicles. Collectively, these results show that FSH and LH stimulate marked increases in the cellular content of Sgk, as well as dramatic changes in the subcellular distribution of this kinase. The specific nuclear vs. cytoplasmic compartmentalization of Sgk in granulosa cells and luteal cells, respectively, indicates that Sgk controls distinct functions in proliferative vs. terminally differentiated granulosa cells.
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P. Yang and S. K. Roy Follicle Stimulating Hormone-Induced DNA Synthesis in the Granulosa Cells of Hamster Preantral Follicles Involves Activation of Cyclin-Dependent Kinase-4 Rather Than Cyclin D2 Synthesis Biol Reprod, February 1, 2004; 70(2): 509 - 517. [Abstract] [Full Text] [PDF] |
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C. Boehmer, V. Wilhelm, M. Palmada, S. Wallisch, G. Henke, H. Brinkmeier, P. Cohen, B. Pieske, and F. Lang Serum and glucocorticoid inducible kinases in the regulation of the cardiac sodium channel SCN5A Cardiovasc Res, March 15, 2003; 57(4): 1079 - 1084. [Abstract] [Full Text] [PDF] |
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A. C. Maiyar, M. L.L. Leong, and G. L. Firestone Importin-alpha Mediates the Regulated Nuclear Targeting of Serum- and Glucocorticoid-inducible Protein Kinase (Sgk) by Recognition of a Nuclear Localization Signal in the Kinase Central Domain Mol. Biol. Cell, March 1, 2003; 14(3): 1221 - 1239. [Abstract] [Full Text] [PDF] |
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S. Chu, S. Rushdi, E.T. Zumpe, P. Mamers, D.L. Healy, T. Jobling, H.G. Burger, and P.J. Fuller FSH-regulated gene expression profiles in ovarian tumours and normal ovaries Mol. Hum. Reprod., May 1, 2002; 8(5): 426 - 433. [Abstract] [Full Text] [PDF] |
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J. D. Stockand New ideas about aldosterone signaling in epithelia Am J Physiol Renal Physiol, April 1, 2002; 282(4): F559 - F576. [Abstract] [Full Text] [PDF] |
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J. S. Richards, S. C. Sharma, A. E. Falender, and Y. H. Lo Expression of FKHR, FKHRL1, and AFX Genes in the Rodent Ovary: Evidence for Regulation by IGF-I, Estrogen, and the Gonadotropins Mol. Endocrinol., March 1, 2002; 16(3): 580 - 599. [Abstract] [Full Text] [PDF] |
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M. Hsieh, M. A. Johnson, N. M. Greenberg, and J. S. Richards Regulated Expression of Wnts and Frizzleds at Specific Stages of Follicular Development in the Rodent Ovary Endocrinology, March 1, 2002; 143(3): 898 - 908. [Abstract] [Full Text] [PDF] |
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J. S. Richards, D. L. Russell, S. Ochsner, M. Hsieh, K. H. Doyle, A. E. Falender, Y. K. Lo, and S. C. Sharma Novel Signaling Pathways That Control Ovarian Follicular Development, Ovulation, and Luteinization Recent Prog. Horm. Res., January 1, 2002; 57(1): 195 - 220. [Abstract] [Full Text] [PDF] |
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F. Lang and P. Cohen Regulation and Physiological Roles of Serum- and Glucocorticoid-Induced Protein Kinase Isoforms Sci. Signal., November 13, 2001; 2001(108): re17 - re17. [Abstract] [Full Text] [PDF] |
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K. H. Burns, C. Yan, T. R. Kumar, and M. M. Matzuk Analysis of Ovarian Gene Expression in Follicle-Stimulating Hormone {beta} Knockout Mice Endocrinology, July 1, 2001; 142(7): 2742 - 2751. [Abstract] [Full Text] [PDF] |
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J. S. Richards Perspective: The Ovarian Follicle--A Perspective in 2001 Endocrinology, June 1, 2001; 142(6): 2184 - 2193. [Full Text] [PDF] |
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J. S. Richards New Signaling Pathways for Hormones and Cyclic Adenosine 3',5'-Monophosphate Action in Endocrine Cells Mol. Endocrinol., February 1, 2001; 15(2): 209 - 218. [Abstract] [Full Text] |
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J. S. Richards Graafian Follicle Function and Luteinization in Nonprimates Reproductive Sciences, January 1, 2001; 8(1_suppl): S21 - S23. [Abstract] [PDF] |
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I. J. Gonzalez-Robayna, A. E. Falender, S. Ochsner, G. L. Firestone, and J. S. Richards Follicle-Stimulating Hormone (FSH) Stimulates Phosphorylation and Activation of Protein Kinase B (PKB/Akt) and Serum and Glucocorticoid-Induced Kinase (Sgk): Evidence for A Kinase-Independent Signaling by FSH in Granulosa Cells Mol. Endocrinol., August 1, 2000; 14(8): 1283 - 1300. [Abstract] [Full Text] |
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S. C. Sharma and J. S. Richards Regulation of AP1 (Jun/Fos) Factor Expression and Activation in Ovarian Granulosa Cells. RELATION OF JunD AND Fra2 TO TERMINAL DIFFERENTIATION J. Biol. Chem., October 20, 2000; 275(43): 33718 - 33728. [Abstract] [Full Text] [PDF] |
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