Inhibition of HCG-Induced Ovarian and Uterine Weight Augmentation in the Immature Rat by Analogs of GnRH

Summary

Experiments were conducted to study the inhibitory effect of large doses of a few analogs of GnRH on ovarian and uterine weight in the immature rat. In most experiments the 21-day-old HCG-primed animal was used. Extensive study of [d-Leu⁶, des-GlyNH₂ ¹⁰, Pro-ethylamide⁹]-GnRH (I) indicated that ovarian weight increase induced by HCG was inhibited in both the intact and hypophysectomized rat. Increasing the augmenting dose of HCG from 50 to 500 IU in the intact animal did not overcome the inhibitory effect of I. Furthermore, twice-a-day injections of I into normal immature rats from 22 to 31 days of age significantly advanced puberty; however, when injections were continued until puberty, vaginal opening was significantly delayed. In general, the inhibitory effect of other analogs of GnRH in the HCG model was proportional to their intrinsic LH and FSH releasing activities. These data constitute direct evidence that large doses of the intensely active analogs of GnRH have inhibitory effects on the ovary, uterus, and reproductive function in the rat.