Insulin Stimulates Androgen Accumulation in Incubations of Ovarian Stroma Obtained from Women with Hyperandrogenism*

The effects of insulin and insulin-like growth factors (IGFs) on ovarian androgen production were examined in ovarian stroma obtained from four women with hyperandrogenism and three women without hyperandrogenism. In incubations of stroma obtained from all four hyperandrogenic patients, insulin alone (500 ng/ml) significantly stimulated androstenedione and testosterone release. LH alone (25 ng/ml) significantly stimulated androstenedione release in incubations of stroma obtained from three of the four hyperandrogenic patients and testosterone release in incubations of stroma obtained from one of the four hyperandrogenic patients. In stromal incubations from three of the four hyperandrogenic patients, insulin alone (500 ng/ml) resulted in a significantly greater release of androstenedione and testosterone than did LH alone (25 ng/ml). Dihydrotestosterone was released in measurable quantities in incubations of stromal tissue obtained from three of the four hyperandrogenic women. In all three instances in which dihydrotestosterone was detectable, insulin alone (500 ng/ml), but not LH alone (25 ng/ml), significantly stimulated dihydrostestosterone release. Incubations of stroma obtained from three nonhyperandrogenic, normally cycling women demonstrated low levels of androstenedione release and negligible testosterone and dihydrotestosterone release. Insulin alone (500 ng/ml) and LH alone (25 ng/ml) produced no significant increase in androstenedione release. Insulin (500 ng/ml) plus LH (25 ng/ml) significantly stimulated androstenedione accumulation in stroma obtained from two of the nonhyperandrogenic women. One insulin dose-response experiment was performed using stromal tissue obtained from a hyperandrogenic woman. In this experiment, insulin, at a dose of 50 ng/ml, was as effective as insulin at a dose of 500 ng/ml in stimulating androstenedione and testosterone release. In addition to insulin, IGF-I/somatomedin C (50 ng/ml) stimulated androstenedione and testosterone release. Relaxin (1 microgram/ml) and multiplication-stimulating activity (50 ng/ml) did not stimulate androstenedione and testosterone release. These studies suggest that human ovarian stroma may be a target tissue for insulin and IGF-I, and that hyperinsulinemia may be an important factor contributing to ovarian hyperandrogenism.