THE EFFECT OF 1-(p-2-DIETHYLAMINOETHOXYPHENYL)-1-PHENYL-2-p-ANISYL ETHANOL UPON RAT PITUITARY AND UTERINE RESPONSES TO ESTROGEN1

Abstract
The pituitary hypertrophy which was readily induced in rats by chronic administration of estradiol valerate was inhibited by the concomitant administration of 1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-anisyl ethanol (MER-25), an analogue of chlorotrianisene. Microscopic examination of the pituitary glands of the animals receiving estrogens showed a chromophobe hyperplasia with no evidence of an associated mammary hypertrophy. The combined administration of MER-25 and estradiol in doses which individually induced 50% gonadotropin inhibition in parabiotic rats resulted in a failure of MER-25 to block the pituitary inhibiting effect of estradiol. The pituitary glands of both the single and parabiotic rats which received only estrogen were found, upon bioassay, to be extraordinarily rich in gonadotropin content. This indicated that estrogen blocks the release rather than the production of gonadotropins. In vitro studies utilizing uterine strips reveal that specimens obtained from spayed rats treated with estradiol and MER-25 showed a decrease in amplitude of contraction as compared to tissues obtained from animals receiving estradiol alone. Interestingly enough, the uterine weights of animals receiving combined injections of MER-25 and estradiol valerate weighed less than the uteri of animals receiving estradiol alone. It may be concluded from these data that MER-25 is an anti-estrogenic compound in some respects but not for all modalities of estrogenic activity.