Biologically Active Substances Affecting Gonadotrophin-Induced Ovulation in Immature Rats

Abstract
The ability of intact or hypophysectomized immature rats to respond to appropriately timed doses of PMS and HCG has been employed as a method of studying the effect of several biologically active compounds in inhibiting ovulation. Single injections of various dose levels of each compound were given at time of HCG injection. Administration of norethynodrel (5 and 10 mg), estradiol (1, 50, 200 and 500 μg), and estrone (0.1, 0.5 and 1.0 mg) resulted in the inhibition of gonadotrophin-induced ovulation, as determined by the significant decrease in the mean number of ova recovered from the fallopian tubes of these animals. Estradiol (0.5 mg) and estrone (0.5 mg) were also capable of inhibiting ovulation under the same conditions in hypophysectomized immature rats, indicating a direct inhibitory action upon the immature ovary. In addition, ovarian weight was decreased in hypophysectomized, gonadotrophinprimed rats treated with either 10 mg norethynodrel or 0.5 mg estradiol, suggesting a direct inhibitory action on the follicular growth induced by exogenous gonadotrophins. Progesterone (1–10 mg), norethindrone (0.1–10.0 mg), testosterone (0.1–5.0 mg), Decadron (0.1 mg), diethylstilbestrol (1–50 Mg), Clomiphene (0.01–0.10 mg), and AY61122 (0.5-5.0 mg) did not inhibit gonadotrophin-induced ovulation in intact rats when given with HCG; the inhibition of normal physiological ovulation in mature rats with these substances is probably the result of their influence on the hypothalamico-hypophysial axis and the pituitary secretion of LH. (Endocrinology75: 359,1964)