HUMAN OVARIAN 17-KETOSTEROID OXIDOREDUCTASE - UNIQUE CHARACTERISTICS OF THE GRANULOSA-LUTEAL CELL AND STROMAL ENZYME

OBJECTIVES: We attempted to test the hypothesis that distinct forms of the 17-ketosteroid oxidoreductase exist in the human ovary and to compare its activity in stroma obtained from normally cycling women and from hyperandrogenic women. STUDY DESIGN: Human ovarian granulosa-luteal cell and stromal 17-ketosteroid oxidoreductase were examined in cell incubations and subcellular homogenates. RESULTS: In subcellular homogenates of granulosa-luteal cells 17-ketosteroid oxidoreductase activity was greater in the cytosol fraction than in the membrane fraction. In contrast, in homogenates of both ovarian stroma and Leydig cells its activity was greater in the membrane fraction than in the cytosol fraction. At the substrate concentrations used estrone was a better substrate than androstenedione for the granulosa-luteal cell 17-ketosteroid oxidoreductase. In contrast, androstenedione was a better substrate than estrone for that in ovarian stromal and Leydig cell membranes. In incubations of ovarian stroma from hyperandrogenic women, significantly more testosterone accumulated in the medium per milligram of tissue than in the medium of incubations of ovarian stroma from normally cycling women (142 +/- 48 vs 7.9 +/- 7.5 pg testosterone per milligram of tissue per 48 hours, mean +/- SD, p < 0.05). The ratio of testosterone to androstenedione was significantly higher in the medium of incubations of ovarian stroma from hyperandrogenic women than in that from normally cycling women (0.61 vs 0.25, mean, p < 0.05). The ratio of serum testosterone to androstenedione was significantly greater in hyperandrogenic women than in normally cycling control women (0.31 +/- 0.11 vs 0.20 +/- 0.03, mean +/- SD, p < 0.05). CONCLUSION: The localization (cytosol fraction) and substrate specificity (estrone) of the granulosa-luteal cell 17-ketosteroid oxidoreductase enzyme resembles that seen in human placenta. The localization (membrane fraction) and substrate specificity (androstenedione) of the ovarian stromal 17-ketosteroid oxidoreductase enzyme resembles that seen in Leydig cells. It may be one enzyme that exists in multiple forms or it may be two (or more) enzymes. In some hyperandrogenic women the ovarian stromal 17-ketosteroid oxidoreductase may be more active than in normally cycling women, contributing to an abnormally increased testosterone production rate.