Co-administration of insulin with a gonadotropin partly improves ovulatory responses of estrogen-deficient mice

Administration of 17-βestradiol (E2) with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) can induce ovulation in estrogen-deficient (ArKO) mice; nevertheless, ovulatory efficiency and rate are low. In this study, effects of insulin on the ovulatory responses were investigated. In ArKO ovary, hCG signal was found to be transmitted in an uncoordinated manner when phosphorylation levels of signaling molecules are examined. Co-administration of insulin with hCG improved the transmission of hCG signal as well as the ovulatory efficiency in ArKO mice. It also improved the ovulatory rate but far below the wild-type rate. Gene expression analysis demonstrated that Cyp11a1 and Cyp17a1 mRNAs were significantly induced 4 h after PMSG administration in the wild-type ovary, but not in ArKO ovary. Collectively, these results suggest that insulin improves ovulatory responses of ArKO mice, but it fails to ameliorate follicular dysfunctions caused possibly by an inappropriate intraovarian milieu during follicular maturation.