EFFECT OF RECOMBINANT INHIBIN ON ANDROGEN SYNTHESIS IN CULTURED HUMAN THECAL CELLS

Effects of inhibin (recombinant human inhibin-A) on ovarian androgen synthesis were tested in vitro using serum-free monolayer cultures of human thecal cells. Treatment for 4 days with inhibin alone at doses between 10 and 100 ng/ml caused modest (approximately 2-fold) increases in production of androgen (androstenedione and dehydroepiandrosterone): similar to the maximal level of stimulation caused by luteinizing hormone (LH) (10 ng/ml) alone but only about one-third of that caused by insulin-like growth factor I (IGF-I) (30 ng/ml) alone. Combined treatment with LH and inhibin elicited additive effects on androgen production whereas LH and IGF-I were synergistic, giving rise to androgen production rates at least 40 times greater than control. Additional presence of inhibin caused up to 10-fold augmentation of the response to LH + IGF-I. Activin (recombinant human activin-A) was previously shown to inhibit LH + IGF-I-induced androgen synthesis in this human thecal cell culture system. In the present study we found that the additional presence of inhibin (> 1 ng/ml) completely neutralized this inhibitory action of activin (10 ng/ml). These effects of inhibin were dose-dependent (ED50 1-10 ng/ml) and maximal at approximately 100 ng/ml. Inhibin stimulation of androgen synthesis occurred in the absence of measurable effects on progesterone production, and cell numbers in cultured cell monolayers were unaltered by the protein. It is concluded that inhibin exerts potent and selective stimulation of human thecal cell androgen synthesis in vitro. These results a paracrine role for inhibin(s) in modulating follicular androgen biosynthesis in the human ovary.