SPECIFICITY OF ESTROGEN-RECEPTORS IN RAT THYMUS

Estrogens exert their effects in reproductive tissues through a primary binding reaction with specific receptor proteins which can be detected and characterized in high speed cytosols. Administered estrogens have profound atrophic effects on the developing thymus and alter thymocyte responsiveness to mitogens in vitro. Estrogen-binding macromolecules have been described in rat thymus cytosol, and an attempt has been made to characterize thoroughly the ligand specificity of these moieties, and compare this with the specificity of the uterus estrogen receptor. Cytosols were prepared from immature rat thymus and uterus and incubated with [H-3]estradiol alone or with one of a range of unlabeled steroids: estradiol-17-alpha (E2-17alpha), estradiol-17-beta (E2-17beta), diethylstilbestrol (DES), estriol (E3), estrone (E1), corticosterone (C), testosterone (T) or progesterone (P). Scatchard plots were derived from the binding isotherms obtained and the molar dissociation constant (K(di)) for each inhibitor measured. In both thymus and uterus, binding of [H-3]estradiol was inhibited most potently by substances possessing estrogen agonist activity, and the rankings of potencies in both tissues were broadly similar, namely: DES>E2-17beta (thymus); DES = E2-17beta (uterus). In both tissues, E2-17beta>E2-17alpha and E3>E1>C>T>P. There were significant differences between thymus and uterus, in that the estrogen receptor in the former tissue exhibited a significantly higher selectivity for some estrogens, including DES and for corticosterone. These differences may underlie differential responsiveness of the two tissues to steroids, and may reflect structural differences between thymus and uterus estrogen receptors.