The Continuing Evolution of an Estrogen-Receptor Model
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A working hypothesis of the mechanism of action of estrogenic hormones similar to that shown in Fig. 1 was first suggested a number of years ago. Reports from our laboratory (1,2) as well as from Elwood Jensen’s (3), suggested that an estrogen-binding protein initially present in the cytosol moved into the nucleus as a result of the interaction with estrogen. The cytoplasmic protein which binds estrogen in uterine cells had all the attributes required of a physiological receptor. These attributes include a highly specific interaction with physiologically active estrogens such as estradiol, diethylstilbestrol, and estriol, but not with androgens, progestins, or glucocorticoids (U,5). The affinity of the estrogens was high, described by the equilibrium dissociation constant as approximately 10-10 to 10-9 M (2), and appropriate for physiological concentrations of estrogens, which are 10-10 to 10-9 M in the plasma of non-pregnant females of most species (6). The binding protein was present in detectable concentrations in the uterus, vagina, other parts of the reproductive tract, and pituitary; but was present in extremely low concentrations in other tissues.
KeywordsNuclear Fraction Nuclear State Estrogen Binding Uterine Cell Estrogen Binding Site
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