Specific binding sites for insulin-like growth factor I in the ovarian stroma of women with polycystic ovarian disease and stromal hyperthecosis. Women with polycystic ovarian disease and hyperthecosis have hyperinsulinemia and insulin resistance. It is possible that insulin in supraphysiologic concentration exerts its steroidogenic action on ovarian stromal cells through insulin-like growth factor I receptors. We undertook this study to investigate whether the ovarian stroma of women with hyperthecosis has specific binding sites for insulin or insulin-like growth factor I. Ovarian stromal tissue was obtained from seven women with normal ovulatory cycles and from five women with hyperthecosis of the ovaries. Binding studies with insulin tagged with iodine 125 and insulin-like growth factor I tagged with iodine 125 revealed specific binding sites both for insulin and insulin-like growth factor I in the ovarian stroma. The binding of insulin tagged with iodine 125 in the ovarian stroma of women with hyperthecosis (3.4% +/- 1.1% (+/- SE) per 100 micrograms protein) was significantly (p less than 0.04) lower than that observed in normal premenopausal women (8.3% +/- 1.6% per 100 micrograms protein). By contrast, the specific binding of insulin-like growth factor I tagged with iodine 125 in the ovarian stroma of women with hyperthecosis (7.1% +/- 1.7% per 100 micrograms protein) was higher than that observed in the ovarian stroma from normal women (4.5% +/- 1.7% per 100 micrograms protein), although the difference was not statistically significant. The affinity constants for these high-affinity receptors were similar (1.2 to 3.6 x 10(9) L/mol) in the two groups of women. These results indicate that (1) the ovarian stroma has specific binding sites both for insulin and for insulin-like growth factor I; (2) in women with hyperthecosis, the ovarian stroma has decreased binding sites for insulin but has normal concentrations of insulin-like growth factor I receptors; and (3) in women with hyperthecosis, stimulation of ovarian androgen synthesis by insulin may be mediated through the insulin-like growth factor I receptors. 