Abstract
The ovulation-inducing effects of synthetic LH-RH and its analogues were studiedin 1) proestrous rats treated with chlorpromazine, 2) persistent estrous rats produced by neonatal treatment with androgen, 3) intact rats at the diestrous stage, and 4) pseudopregnant rats produced by treatment with estrogen, and the gonadotrophic responses of ovaries and follicles in these animals were examined. The results obtained were as followes: 1) Histological examination revealed that theovaries of the animals in the respective groups before treatment with LH-RH contained comparable populations of small- and large-sized follicles, but the population of largesized follicles tended to decrease in the following order: persistent estrous, proestrous, diestrous, and pseudopregnant rats. 2) Both subcutaneousand intravenous injections of human chorionic gonadotrophin into the animals of the respective groups induced ovulation effectively. However, the ovulating responses in terms of the threshold dose differed among the respective groups two-fold in the subcutaneous route and three- to seven-fold in the intravenous route. 3) LH-RH and its analogues administered subcutaneously or intravenously in the animals of the respective groups induced dose-dependent ovulation. Proestrous rats were the most sensitive and pseudopregnant rats were the least sensitive to the subcutaneous or intravenous injection of LH-RH. When the sensitivity of pseudopregnant rats to LH-RH was taken as 1 in terms of the reciprocal of the subcutaneous ED50s, the relative sensitivities of proestrous, persistent estrous, and diestrous animals were 950, 500, and 110, respectively. Among the analogues examined, des-G1y10-[D-Leu6]-LH-RH-ethylamide was the most effective and also much more effective than LH-RH. The relative sensitivities to this analogue in proestrous, persistent estrous, and diestrous rats to pseudopregnant rats through the subcutaneous route were 12.8, 5.4, and 4.3, respectively.
