Action of an estrogen antagonist on reproductive mechanisms in the rat.

A nonsteroidal compound (CN-55, 945-27) was found to inhibit uterine responsiveness to 17β-estradiol and to stimulate LH secretion when administered orally (25 μg/kg) to adult intact rats. Since the compound was not observed to prevent the blastocyst per se from implanting and developing normally, these effects may account for its ability to prevent pregnancy when given daily (25 μg/kg) or as a single dose (500 μg/kg) post coitus. That is, the compound may inhibit implantation mechanisms, which in the rat require estrogen and a functional corpus luteum, by antagonizing the action of estrogen and/or stimulating the release of LH (luteolytic action in the rat). The fact that CN-55,945-27 inhibited the decidual response in adult intact rats is consistent with the conclusion that the compound exerts its antifertility activity by blocking implantation. The compound showed no direct action on the ovary in terms of affecting growth, steroidogenesis or ovulation. It did exhibit, under various experimental conditi...