Temporal Relationship Between the Abortifacient Effects of GnRH Antagonists and Hormonal Secretion

Abstract

Two GnRH antagonists, [Ac-Δ³-Pro¹, pCl-D-Phe², D-Trp^3,6, N^αMeLeu⁷]-GnRH and [Ac-Δ³-Pro¹, pF-D-Phe², D-Trp^3,6]-GnRH, were administered to female rats during various stages of pregnancy. Administration of these antagonists during the first week of pregnancy terminated gestation in ∿50% of animals, in which case it was accompanied by a drop in circulating LH, but very little change in progesterone, estradiol, and PRL levels. Treatment periods encompassing Days 7 to 12 were more effective in lowering plasma LH and P_O, as well as in causing abortion. No abortifacient effect was observed when the peptides were injected after Day 12. Concomitant administration of progesterone during Weeks 1 or 2 after mating completely reversed the effects of the antagonists. These data indicate that GnRH antagonists exert maximal antireproductive effects when administered at the time of LH-dependency of the corpus luteum.