Effects of two estradiol antagonists upon the estradiol uptake in the rat brain and peripheral tissues.

Two estradiol antagonists, Parke-Davis CI 628 and CI 680, were studied for their inhibitory potency against labeled estradiol uptake within the hypothalamus, cerebral cortex, pituitary and uterus of the ovariectomized rat. Both drugs, tested from 15 min to 24 h prior to estradiol, induced a fast and long-lasting decrease of the hormone uptake. Three degrees of inhibition were observed depending on the tissue studied: (a) the most important inhibition concerned uterus and pituitary, where the estradiol uptake was prevented by up to 90% by the largest doses of antagonists used (6.3 and 6.1 mg, respectively, for CI 268 and CI 680); (b) in the hypothalamus, the estradiol uptake was counteracted to a lower degree; the inhibition being 39% for anterior hypothalamus and 22% for medial posterior hypothalamus; (c) cerebral cortex uptake was completely unaffected by pretreatments with the antagonists. After subcellular fractionation it was observed that the nuclear uptake of estradiol was completely abolished in both hypophyseal and hypothalamic tissues if the hormonal injection was preceded by the administration of 6.3 mg of CI 628.