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Molecular Endocrinology 13 (6): 946-957
Copyright © 1999 by The Endocrine Society

Augmented Androgen Production Is a Stable Steroidogenic Phenotype of Propagated Theca Cells from Polycystic Ovaries

Velen L. Nelson, Richard S. Legro, Jerome F. Strauss, III and Jan M. McAllister

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 Women’s 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{alpha}-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{alpha}-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. Clin. Endocrinol. Metab., June 1, 2000; 85(6): 2304 - 2311.
[Abstract] [Full Text]


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EndocrinologyHome page
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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J. Clin. Endocrinol. Metab.Home page
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.
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Mol. Endocrinol.Home page
J. F. Strauss III and A. Dunaif
Molecular Mysteries of Polycystic Ovary Syndrome
Mol. Endocrinol., June 1, 1999; 13(6): 800 - 805.
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Proc. Natl. Acad. Sci. USAHome page
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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