Clomiphene citrate inhibits gonadotropin-induced ovulation by reducing cyclic adenosine 3′,5′-cyclic monophosphate and prostaglandin E2 levels in rat ovary

Objective To determine whether clomiphene citrate (CC) inhibited gonadotropin-induced ovulation by reducing cyclic adenosine 3′,5′-cyclic monophosphate (cAMP) and prostaglandin E 2 (PGE 2 ) levels in ovary. If so, to determine whether E 2 coadministration could protect against these effects of CC. Design A controlled prospective study. Setting Laboratory research setting in the department of reproductive biomedicine at a national research institute in India. Animal(s) Sixty sexually immature female rats that were 24–25 days of age. Intervention(s) The sexually immature female rats were given a single injection (10 IU IM) of pregnant mare serum gonadotropin. After 48 hours, the rats were given single injections of hCG (10 IU) along with CC, with or without E 2 , for 16 hours. Main Outcome Measure(s) Number of superovulated COCs, ovary and uterus weight, FSH and LH levels in serum, and cAMP and PGE 2 levels in ovary. Result(s) The superovulatory dose of gonadotropins significantly increased ovary and uterus weights, cAMP and PGE 2 levels in ovary, and serum levels of FSH and LH. Coadministration of CC (10 mg/kg body weight) significantly reduced levels of cAMP, PGE 2 in the ovary, ovary and uterus weights, and ovulation rate, whereas FSH and LH levels were not significantly altered. Supplementation of E 2 protected against these inhibitory effects of CC and augmented levels of FSH and LH in serum. Conclusion(s) Clomiphene citrate inhibited gonadotropin-induced ovulation by reducing cAMP and PGE 2 levels in the ovary, and E 2 protected against these effects of CC on gonadotropin-induced ovulation in rat.