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): Six 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 rates, whereas LSH and LH levels were not significantly altered. Supplementaion 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.