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 micrograms/kg, effectively inhibited the initiation of embryo implantation in rats when administered on day 4 of pregnancy (day 1 = sperm positive). The same dose inhibited the implantation initiating effect of intravenous 25 ng of estradiol-17 beta in delayed implanting progesterone-primed hypophysectomized rats. In contrast, the anti-estrogen at a dose of 1 mg/kg was ineffective at inhibiting the initiation of implantation induced by intrauterine plus intravenous administration of murine epidermal growth factor to delayed implanting rats. The growth factor also initiated implantation of blastocysts transferred from donor animals injected with the anti-estrogen to progesterone-primed hypophysectomized recipients. The results clearly demonstrate that the implantation initiating effect of the growth factor is not inhibited by a pure estrogen antagonist, and therefore this estrogenic function does not appear to require action initiated by the classical estrogen receptor.