CONTRASTING ACTION OF ANTIESTROGEN (ICI-182780) FOR PREVENTING INITIATION OF EMBRYO IMPLANTATION BY ESTRADIOL OR EPIDERMAL GROWTH-FACTOR (EGF)

The pure estrogen antagonist ICI-182780, at doses above 50 mug/kg, eff ectively inhibited the initiation of embryo implantation in rats when administered on day 4 of pregnancy (day 1=sperm positive) . The same d ose inhibited the implantation initiating effect of intravenous 25 ng of estradiol-17beta in delayed implanting progesterone-primed hypophys ectomized rats. In contrast, the anti-estrogen at a dose of 1 mg/kg wa s ineffective at inhibiting the initiation of implantation induced by intrauterine plus intravenous administration of murine epidermal growt h factor to delayed implanting rats. The growth factor also initiated implantation of blastocysts transferred from donor animals injected wi th the anti-estrogen to progesterone-primed hypophysectomized recipien ts. The results clearly demonstrate that the implantation initiating e ffect of the growth factor is not inhibited by a pure estrogen antagon ist, and therefore this estrogenic function does not appear to require action initiated by the classical estrogen receptor.