5α-Reductase Activity in Women with Polycystic Ovary Syndrome1

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