Regulation of human ovarian insulin receptors in vivo

Abstract

Insulin participates in regulating ovarian function in normal and in pathological states. This effect of insulin may be mediated by ovarian insulin receptors. We have previously characterized human ovarian insulin receptors and began to examine their regulation in vitro. The present study examines regulation of human ovarian insulin receptors in vivo. Stromal ovarian tissue was obtained from 21 women during an indicated surgical procedure. Ten women were premenopausal and 11 were postmenopausal. Specific 125I-insulin binding to stromal ovarian fragments ranged from 2.5% to 7.3%/mg protein. 125I-insulin binding to stromal fragments correlated positively with 125I-insulin binding to circulating leucocytes (r = .57; P < .01). When postmenopausal and premenopausal women were analyzed separately, this relationship persisted in postmenopausal women (r = .70; P < .05), but not in premenopausal women. 125I-insulin binding to stromal overian fragments correlated negatively with age (r = −.63; P = .005). 125I-insulin binding to stromal ovarian fragments tended to correlate negatively with plasma insulin levels in postmenopausal women (r = −.67; P = .06), but not in premenopausal women. Plasma insulin levels correlated negatively with serum SHBG (r = − .62; P = .003). The percent free testosterone levels correlated positively with plasma insulin levels in premenopausal women (r = .95; P = .0001), but not in postmenopausal women. Our findings demonstrate that (1) ovarian 125I-insulin binding correlates well with 125I-insulin binding to circulating white cells, suggesting that insulin is an important regulator of ovarian insulin receptors, particularly after the menopause; (2) the lack of correlation between 125I-insulin binding to circulating white cells and to ovarian stromal fragments from premenopausal women suggests that factors other than insulin participate in insulin-receptor regulation in premenopausal ovaries; (3) the number of ovarian insulin receptors decreases with age; and (4) insulin inhibits SHBG production in premenopausal women, thereby increasing the biologic availability of testosterone. These findings are important in understanding the nature of ovarian dysfunction in such diverse entities as diabetes mellitus, syndromes of insulin resistance, obesity, and polycystic ovarian syndrome.