Differential stimulation by 17 beta-estradiol and synthetic estrogens of progesterone-receptor and of translocation of estrogen-receptor in rat pituitary and uterus.

Central and peripheral actions of physiological and synthetic estrogens with elevated biological potencies were investigated. The synthetic estrogens were 1,3-diacetoxy-17 alpha-ethinyl-7 alpha-methyl-1,3,5(10)-estratrien-17 beta-ol (DM-EE2) and 1,3-dibenzoyloxy-17 alpha-ethinyl-7 alpha-methyl-1,3,5(10)-estratrien-17 beta-ol (DB-EE2). More prolonged nuclear retention of the estrogen-receptor was found after application of DM-EE2 and DB-EE2, than in the pituitary and uterus after injection of the same dose of 17 beta-estradiol (E2). Longer nuclear retention of the estrogen-receptor was observed in the pituitary after DB-EE2 application and in the uterus after DM-EE2 than in E2-treated rats. Pituitary progesterone-receptor was raised to 706% of controls by treatment with E2 and 1187% and 2308% after injection of DM-EE2 and DB-EE2, respectively. On the other hand, only 208% and 225% stimulation, respectively, of progesterone-receptor was observed in the uterus after treatment with the synthetic estrogens DM-EE2 and DB-EE2. In vitro cytosol receptor binding assays revealed low relative binding affinities of the synthetic estrogens compared to E2. The results may be explained by the hypothesis that differences in biological activity of estrogens may be caused by different metabolic and/or cellular events localized in distinct target organs or by altered affinity of the nuclear estrogen receptor complex to chromatin receptor sites due to a change in receptor conformation.