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

ObjectiveTo determine whether clomiphene citrate (CC) inhibited gonadotropin-induced ovulation by reducing cyclic adenosine 3′,5′-cyclic monophosphate (cAMP) and prostaglandin E2 (PGE2) levels in ovary. If so, to determine whether E2 coadministration could protect against these effects of CC.DesignA controlled prospective study.SettingLaboratory 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 E2, for 16 hours.Main Outcome Measure(s)Number of superovulated COCs, ovary and uterus weight, FSH and LH levels in serum, and cAMP and PGE2 levels in ovary.Result(s)The superovulatory dose of gonadotropins significantly increased ovary and uterus weights, cAMP and PGE2 levels in ovary, and serum levels of FSH and LH. Coadministration of CC (10 mg/kg body weight) significantly reduced levels of cAMP, PGE2 in the ovary, ovary and uterus weights, and ovulation rate, whereas FSH and LH levels were not significantly altered. Supplementation of E2 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 PGE2 levels in the ovary, and E2 protected against these effects of CC on gonadotropin-induced ovulation in rat.