Antireproductive Effects of a Potent GnRH Antagonist in the Female Rat*

Abstract

The administration of the potent gonadotropinreleasing hormone antagonist [Ac-dehydro-Pro¹,pCl-D-Phe²,DTrp^3,6, N^αeLeu⁷]GnRH (Antag) to female rats results in disruption of the estrous cycle and gestation. Daily doses of 200 μg Antag are completely effective in blocking regular cycles, which resume 6–9 days after cessation of treatment. When administered to mated female rats, Antag seems to be less effective in terminating pregnancy during the earlier (1–7 days) than later (7–12 days) days of gestation. This may reflect the inability of An tag to lower the secretion of PRL (the luteotropic hormone of early pregnancy) as compared to the Antag-induced inhibition of LH production (the luteotropic hormone of midpregnancy). As a result, administration of Antag 7–12 days after mating is accompanied by a decrease in plasma progesterone levels incompatible with the survival of the embryos. These data provide further evidence that the neutralization of the function of endogenous gonadotropin-releasing hormone is deleterious to reproductive integrity.