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5-Reductase Activity in Women with Polycystic Ovary Syndrome¹

Department of Obstetrics and Gynecology, Cedars-Sinai Burns and Allen Research Institute, Cedars-Sinai Medical Center/University of California School of Medicine (S.R.W., D.A.M.), Los Angeles, California 90048; and the Department of Obstetrics and Gynecology, Second Clinic of Surgical Gynecology, University School of Medicine (A.J.J.), 20-090 Lublin, Poland

Address all correspondence and requests for reprints to: Dr. Denis A. Magoffin, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048. E-mail: magoffin{at}cshs.org

The recent demonstration of high concentrations of 5-androstane-3,17-dione in the follicular fluid of polycystic ovaries suggests a potential role for 5-reduced androgens in the etiology of polycystic ovary syndrome (PCOS). The purpose of the present study was to determine whether there is increased 5-reductase activity or messenger ribonucleic acid (mRNA) expression in polycystic ovaries. 5-Reductase 1 and 5-reductase 2 mRNAs were measured in thecal (TC) and granulosa (GC) cells from individual follicles of 18 women with PCOS and 26 regularly cycling control women. Both 5-reductase 1 and 2 mRNA expression was higher in GC than in TC, and 5-reductase 2 mRNA levels were approximately 3-fold higher than 5-reductase 1 mRNA. 5-Reductase 1 and 2 mRNA expression were similar in GC from PCOS and control women, but 5-reductase mRNA was decreased in TC from PCOS follicles. In control women, 5-reductase 2 mRNA was highest in GC from 3- to 5-mm follicles and decreased to undetectable levels in GC from 7-mm follicles. A similar pattern of expression was present in GC from PCOS follicles, but detectable levels of 5-reductase 2 mRNA were present in GC from 7-mm follicles. 5-Reductase activity was measured in whole follicles by measuring the conversion of radiolabeled testosterone to dihydrotestosterone. Kinetic analysis of total 5-reductase activity at physiological pH revealed a K_m of 1.46 µmol/L and a maximal velocity of 0.31 nmol/min·mg protein, indicating predominantly type 1 activity. The total 5-reductase activity was approximately 4-fold higher in PCOS follicles than in control follicles. These data demonstrate elevated 5-reductase activity in polycystic ovaries and support the hypothesis that 5-reduced androgens may play a role in the pathogenesis of PCOS.

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