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Department of Cellular and Molecular Physiology (V.L.N.,
J.M.M.) and Department of Obstetrics and Gynecology (R.S.L.)
Pennsylvania State University College of Medicine Hershey,
Pennsylvania 17033
Center for Research on Reproduction and
Womens Health University of Pennsylvania (J.F.S.)
Philadelphia, Pennsylvania 19104
To test the hypothesis that the hyperandrogenemia
associated with polycystic ovary syndrome (PCOS) results from an
intrinsic abnormality in ovarian theca cell steroidogenesis, we
examined steroid hormone production, steroidogenic enzyme activity, and
mRNA expression in normal and PCOS theca cells propagated in long-term
culture. Progesterone (P4), 17
-hydroxyprogesterone (17OHP4),
and testosterone (T) production per cell were markedly increased
in PCOS theca cell cultures. Moreover, basal and forskolin-stimulated
pregnenolone, P4, and dehydroepiandrosterone metabolism were increased
dramatically in PCOS theca cells. PCOS theca cells were capable of
substantial metabolism of precursors into T, reflecting expression of
an androgenic 17ß-hydroxysteroid dehydrogenase. Forskolin-stimulated
cholesterol side chain cleavage enzyme (CYP11A) and
17
-hydroxylase/17,20-desmolase (CYP17) expression were augmented in
PCOS theca cells compared with normal cells, whereas no differences
were found in steroidogenic acute regulatory protein mRNA
expression. Collectively, these observations establish that
increased CYP11A and CYP17 mRNA expression, as well as increased CYP17,
3ß-hydroxysteroid dehydrogenase, and 17ß-hydroxysteroid
dehydrogenase enzyme activity per theca cell, and consequently
increased production of P4, 17OHP4, and T, are stable properties of
PCOS theca cells. These findings are consistent with the notion
that there is an intrinsic alteration in the steroidogenic activity of
PCOS thecal cells that encompasses multiple steps in the biosynthetic
pathway.
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J. R. Wood, V. L. Nelson, C. Ho, E. Jansen, C. Y. Wang, M. Urbanek, J. M. McAllister, S. Mosselman, and J. F. Strauss III The Molecular Phenotype of Polycystic Ovary Syndrome (PCOS) Theca Cells and New Candidate PCOS Genes Defined by Microarray Analysis J. Biol. Chem., July 11, 2003; 278(29): 26380 - 26390. [Abstract] [Full Text] [PDF] |
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M. Fassnacht, N. Schlenz, S. B. Schneider, S. A. Wudy, B. Allolio, and W. Arlt Beyond Adrenal and Ovarian Androgen Generation: Increased Peripheral 5{alpha}-Reductase Activity in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2760 - 2766. [Abstract] [Full Text] [PDF] |
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J. F. Couse, M. M. Yates, V. R. Walker, and K. S. Korach Characterization of the Hypothalamic-Pituitary-Gonadal Axis in Estrogen Receptor (ER) Null Mice Reveals Hypergonadism and Endocrine Sex Reversal in Females Lacking ER{alpha} But Not ER{beta} Mol. Endocrinol., June 1, 2003; 17(6): 1039 - 1053. [Abstract] [Full Text] [PDF] |
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L. B. Lutz, M. Jamnongjit, W.-H. Yang, D. Jahani, A. Gill, and S. R. Hammes Selective Modulation of Genomic and Nongenomic Androgen Responses by Androgen Receptor Ligands Mol. Endocrinol., June 1, 2003; 17(6): 1106 - 1116. [Abstract] [Full Text] [PDF] |
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A. J. Jakimiuk, S. R. Weitsman, A. Navab, and D. A. Magoffin Luteinizing Hormone Receptor, Steroidogenesis Acute Regulatory Protein, and Steroidogenic Enzyme Messenger Ribonucleic Acids Are Overexpressed in Thecal and Granulosa Cells from Polycystic Ovaries J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1318 - 1323. [Abstract] [Full Text] |
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J. W. M. Martens, D. H. Geller, W. Arlt, R. J. Auchus, V. S. Ossovskaya, H. Rodriguez, A. Dunaif, and W. L. Miller Enzymatic Activities of P450c17 Stably Expressed in Fibroblasts from Patients with the Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4338 - 4346. [Abstract] [Full Text] |
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G. Zhang, J. C. Garmey, and J. D. Veldhuis Interactive Stimulation by Luteinizing Hormone and Insulin of the Steroidogenic Acute Regulatory (StAR) Protein and 17{alpha}-Hydroxylase/17, 20-Lyase (CYP17) Genes in Porcine Theca Cells Endocrinology, August 1, 2000; 141(8): 2735 - 2742. [Abstract] [Full Text] [PDF] |
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J. K. Wickenheisser, P. G. Quinn, V. L. Nelson, R. S. Legro, J. F. Strauss III, and J. M. McAllister. Differential Activity of the Cytochrome P450 17{alpha}-Hydroxylase and Steroidogenic Acute Regulatory Protein Gene Promoters in Normal and Polycystic Ovary Syndrome Theca Cells J. Clin. Endocrinol. Metab., June 1, 2000; 85(6): 2304 - 2311. [Abstract] [Full Text] |
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G. A. Dissen, H. E. Lara, V. Leyton, A. Paredes, D. F. Hill, M. E. Costa, A. Martinez-Serrano, and S. R. Ojeda Intraovarian Excess of Nerve Growth Factor Increases Androgen Secretion and Disrupts Estrous Cyclicity in the Rat Endocrinology, March 1, 2000; 141(3): 1073 - 1082. [Abstract] [Full Text] [PDF] |
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B. Imani, M. J. C. Eijkemans, F. H. de Jong, N. N. Payne, P. Bouchard, L. C. Giudice, and B. C. J. M. Fauser Free Androgen Index and Leptin Are the Most Prominent Endocrine Predictors of Ovarian Response during Clomiphene Citrate Induction of Ovulation in Normogonadotropic Oligoamenorrheic Infertility J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 676 - 682. [Abstract] [Full Text] |
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J. F. Strauss III and A. Dunaif Molecular Mysteries of Polycystic Ovary Syndrome Mol. Endocrinol., June 1, 1999; 13(6): 800 - 805. [Full Text] |
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L. B. Lutz, L. M. Cole, M. K. Gupta, K. W. Kwist, R. J. Auchus, and S. R. Hammes Evidence that androgens are the primary steroids produced by Xenopus laevis ovaries and may signal through the classical androgen receptor to promote oocyte maturation PNAS, November 20, 2001; 98(24): 13728 - 13733. [Abstract] [Full Text] [PDF] |
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