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Original Studies |
Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical College of Virginia/Virginia Commonwealth University (J.E.N.), Richmond, Virginia 23298; and Hospital de Clinicas Caracas (D.J.J., A.F.V., C.B., N.Q., F.M.), Caracas, Venezuela
Address all correspondence and requests for reprints to: John E. Nestler, M.D., Medical College of Virginia, P.O. Box 980111, Richmond, Virginia 23298-0111. E-mail: nestler{at}hsc.vcu.edu
To determine whether insulin stimulates human ovarian testosterone
production in the polycystic ovary syndrome by activating its own
receptor and using inositolglycan mediators as the signal transduction
system, thecal cells from polycystic ovary syndrome women were isolated
and cultured. Insulin and insulin-like growth factor I stimulated
thecal testosterone biosynthesis. Antibody blockade of the insulin
receptor abolished insulin’s stimulatory action, whereas effective
antibody blockade of the insulin-like growth factor I receptor did not
alter insulin’s stimulation of thecal testosterone biosynthesis. A
chiro-inositol containing glycan (INS-2) increased thecal testosterone
biosynthesis. Preincubation of cells with an antiinositolglycan
antibody (A23939 or 
IGP) abolished insulin’s stimulatory effect,
but not that of hCG. These findings suggest that inositolglycans serve
as the signal transduction system for insulin’s stimulation of human
thecal testosterone biosynthesis.
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R. S. Legro, R. Azziz, D. Ehrmann, A. G. Fereshetian, M. O'Keefe, and M. N. Ghazzi Minimal Response of Circulating Lipids in Women with Polycystic Ovary Syndrome to Improvement in Insulin Sensitivity with Troglitazone J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5137 - 5144. [Abstract] [Full Text] [PDF]
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C. A. Eagleson, A. B. Bellows, K. Hu, M. B. Gingrich, and J. C. Marshall Obese Patients with Polycystic Ovary Syndrome: Evidence that Metformin Does Not Restore Sensitivity of the Gonadotropin-Releasing Hormone Pulse Generator to Inhibition by Ovarian Steroids J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5158 - 5162. [Abstract] [Full Text] [PDF]
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D. Seto-Young, J. Zajac, H.-C. Liu, Z. Rosenwaks, and L. Poretsky The Role of Mitogen-Activated Protein Kinase in Insulin and Insulin-Like Growth Factor I (IGF-I) Signaling Cascades for Progesterone and IGF-Binding Protein-1 Production in Human Granulosa Cells J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3385 - 3391. [Abstract] [Full Text] [PDF]
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F. C. W. Wu and A. von Eckardstein Androgens and Coronary Artery Disease Endocr. Rev., April 1, 2003; 24(2): 183 - 217. [Abstract] [Full Text] [PDF]
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 R. Kaaks, A. Lukanova, and M. S. Kurzer Obesity, Endogenous Hormones, and Endometrial Cancer Risk: A Synthetic Review Cancer Epidemiol. Biomarkers Prev., December 1, 2002; 11(12): 1531 - 1543. [Abstract] [Full Text] [PDF]
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M. E. Silfen, C. H. L. Shackleton, A. M. Manibo, L. S. Levine, D. Sekhar, D. J. McMahon, and S. E. Oberfield 5{alpha}-Reductase and 11{beta}-Hydroxysteroid Dehydrogenase Activity in Prepubertal Hispanic Girls with Premature Adrenarche J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4647 - 4651. [Abstract] [Full Text] [PDF]
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T. Itoh, M. Kacchi, H. Abe, Y. Sendai, and H. Hoshi Growth, Antrum Formation, and Estradiol Production of Bovine Preantral Follicles Cultured in a Serum-Free Medium Biol Reprod, October 1, 2002; 67(4): 1099 - 1105. [Abstract] [Full Text] [PDF]
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S. A. Arslanian, V. Lewy, K. Danadian, and R. Saad Metformin Therapy in Obese Adolescents with Polycystic Ovary Syndrome and Impaired Glucose Tolerance: Amelioration of Exaggerated Adrenal Response to Adrenocorticotropin with Reduction of Insulinemia/Insulin Resistance J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1555 - 1559. [Abstract] [Full Text] [PDF]
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J. D. Veldhuis, G. Zhang, and J. C. Garmey Troglitazone, an Insulin-Sensitizing Thiazolidinedione, Represses Combined Stimulation by LH and Insulin of de Novo Androgen Biosynthesis by Thecal Cells in Vitro J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1129 - 1133. [Abstract] [Full Text] [PDF]
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M. E. Silfen, A. M. Manibo, M. Ferin, D. J. McMahon, L. S. Levine, and S. E. Oberfield Elevated Free IGF-I Levels in Prepubertal Hispanic Girls with Premature Adrenarche: Relationship with Hyperandrogenism and Insulin Sensitivity J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 398 - 403. [Abstract] [Full Text] [PDF]
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T. Sir-Petermann, L. Devoto, M. Maliqueo, P. Peirano, S.E. Recabarren, and L. Wildt Resumption of ovarian function during lactational amenorrhoea in breastfeeding women with polycystic ovarian syndrome: endocrine aspects Hum. Reprod., August 1, 2001; 16(8): 1603 - 1610. [Abstract] [Full Text] [PDF]
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L. Poretsky, D. Seto-Young, A. Shrestha, S. Dhillon, M. Mirjany, H.-C. Liu, M. C Yih, and Z. Rosenwaks Phosphatidyl-Inositol-3 Kinase-Independent Insulin Action Pathway(s) in the Human Ovary J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3115 - 3119. [Abstract] [Full Text] [PDF]
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R. Azziz, D. Ehrmann, R. S. Legro, R. W. Whitcomb, R. Hanley, A. G. Fereshetian, M. O’Keefe, and M. N. Ghazzi Troglitazone Improves Ovulation and Hirsutism in the Polycystic Ovary Syndrome: A Multicenter, Double Blind, Placebo-Controlled Trial J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1626 - 1632. [Abstract] [Full Text]
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D. J. Jakubowicz, M. Seppälä, S. Jakubowicz, O. Rodriguez-Armas, A. Rivas-Santiago, H. Koistinen, R. Koistinen, and J. E. Nestler Insulin Reduction with Metformin Increases Luteal Phase Serum Glycodelin and Insulin-Like Growth Factor-Binding Protein 1 Concentrations and Enhances Uterine Vascularity and Blood Flow in the Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1126 - 1133. [Abstract] [Full Text]
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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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N. Sekar, H. A. LaVoie, and J. D. Veldhuis Concerted Regulation of Steroidogenic Acute Regulatory Gene Expression by Luteinizing Hormone and Insulin (or Insulin-Like Growth Factor I) in Primary Cultures of Porcine Granulosa-Luteal Cells Endocrinology, November 1, 2000; 141(11): 3983 - 3992. [Abstract] [Full Text] [PDF]
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L. Ibáñez, C. Valls, N. Potau, M. V. Marcos, and F. de Zegher Sensitization to Insulin in Adolescent Girls to Normalize Hirsutism, Hyperandrogenism, Oligomenorrhea, Dyslipidemia, and Hyperinsulinism after Precocious Pubarche J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3526 - 3530. [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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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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C.-B. Book and A. Dunaif Selective Insulin Resistance in the Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3110 - 3116. [Abstract] [Full Text]
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L. Poretsky, N. A. Cataldo, Z. Rosenwaks, and L. C. Giudice The Insulin-Related Ovarian Regulatory System in Health and Disease Endocr. Rev., August 1, 1999; 20(4): 535 - 582. [Abstract] [Full Text] [PDF]
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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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V. L. Nelson, R. S. Legro, J. F. Strauss III, and J. M. McAllister Augmented Androgen Production Is a Stable Steroidogenic Phenotype of Propagated Theca Cells from Polycystic Ovaries Mol. Endocrinol., June 1, 1999; 13(6): 946 - 957. [Abstract] [Full Text]
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