Antireproductive effects of a potent GnRH antagonist in the female rat

The administration of the potent gonadotropin-releasing hormone antagonist [Ac-dehydro-Pro1,pCl-D-Phe2,D-Trp3,6,N alpha MeLeu7]GnRH (Antag) to female rats results in disruption of the estrous cycle and gestation. Daily doses of 200 microgram 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 Antag 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.