Insulin has a biphasic effect on the ability of human chorionic gonadotropin to induce ovarian cysts in the rat

Hyperinsulinemia enhances the ability of subovulatory doses of human chorio nic gonadotropin (hCG) to induce ovarian follicular cysts in the rat. To de termine the relative contribution of these hormones to the development of o varian cysts, adult female rats were treated with either (1) vehicle alone (controls), (2) a high-fat diet (HFD) to control for the effects of weight gain, (3) 1.5 to 6 IU hCG twice daily plus 6 U insulin (Ins)/d, or (4) 1.5 to 9 U Ins/d plus 3 IU hCG twice daily. On day 23 of the in vivo treatments , all groups that received at least 6 U Ins/d displayed increased body weig ht compared with control and HFD rats (P less than or equal to .05), No con trol rats and only one HFD rat displayed ovarian cysts on this day. Plasma estrone (El) and androstenedione (A4) were elevated in HFD rats with noncys tic follicles compared with control rats (P less than or equal to .05). Bet ween 64% and 80% of rats on 6 U Ins/d plus twice-daily injections of 1.5 to 6 IU hCG displayed ovarian cysts on day 23, Plasma estradiol (E2) concentr ations for these treatment groups were similar to those of control rats. Of the hormonally treated animals, only those that had ovarian cysts in respo nse to twice-daily injections of 4.5 or 6 IU hCG plus 6 U Ins/d displayed e levated plasma A4 and/or testosterone compared with controls. In contrast, plasma El concentrations were elevated on day 23 for animals hearing ovaria n cysts in response to increasing doses of hCG plus the fixed dose of 6 U I ns/d. Between 70% and 80% of rats treated twice daily with 3 IU hCG plus a daily dose of 1.5 to 6 U Ins displayed ovarian cysts on day 23. In marked c ontrast, only 25% of rats treated with this dose of hCG plus 9 U Ins/d deve loped cystic follicles. Of the plasma steroids tested, only El and A4 were elevated in these treatment groups compared with controls. However, these i ncreases in plasma steroid concentrations did not correlate with the dose o f insulin. We conclude from these data that, although the mechanisms remain to be elucidated, extreme hyperinsulinemia has the paradoxical ability to attenuate the induction of ovarian cysts by hCG in some animals. Copyright (C) 1999 by W.B. Saunders Company.