Resistin stimulation of 17α-hydroxylase activity in ovarian theca cells in Vitro: Relevance to polycystic ovary syndrome

Context: A newly discovered hormone resistin has been shown to be increased in women with polycystic ovary syndrome (PCOS). Objective: The purpose of this study was to confirm increased resistin concentrations in women with PCOS and to test the direct effect of resistin on human theca cell androgen production. Design: Resistin was measured in fasting serum samples by RIA. To test the direct effects of resistin on ovarian androgen biosynthesis, human theca cells were cultured with resistin for 3 d in the presence and absence of forskolin and insulin. Patients: Fasting serum samples were obtained from 45 women with PCOS and 74 regularly cycling premenopausal control women in the follicular phase of their menstrual cycles, and ovarian theca cell cultures were established from two control women. Results: The mean serum resistin concentration was increased (40%) in women with PCOS. Serum resistin concentrations correlated positively with body mass index and testosterone in PCOS women but not in controls. There were no significant correlations between resistin and fasting insulin or indicators of insulin resistance when corrected for body mass index. In cultured human theca cells, basal 17α-hydroxylase activity was unchanged by resistin alone, but resistin enhanced 17α-hydroxylase activity in the presence of forskolin or a combination of forskolin plus insulin. Resistin (≥1 ng/ml) augmented forskolin and forskolin plus insulin stimulation of CYP17 mRNA expression in a concentration-dependent manner. Conclusion: These data indicate that abnormal resistin secretion in PCOS may play a role in causing ovarian hyperandrogenism.