Estriol and estrone interaction with the estrogen receptor. II. Estriol and estrone-induced inhibition of the cooperative binding of [3H]estradiol to the estrogen receptor.
Kinetic analysis of the estrogen receptor's cooperative equilibrium [3H]estradiol binding (Sasson, S., and Notides, A. C., (1982) J. Biol. Chem. 257, 11540-11545) provides a sensitive method for probing the binding of partial agonists to the estrogen receptor. We studied the effects of estriol and estrone on the positive cooperativity of [3H]estradiol binding to the partially purified, calf uterine estrogen receptor. The receptor was titrated with variable concentrations of [3H]estradiol in combination with estriol or estrone, while maintaining a constant molar ratio of the estriol or estrone to the [3H]estradiol. With either a 4-fold molar excess of estriol or a 25-fold molar excess of estrone above the [3H]estradiol concentrations, the receptor's positive cooperative [3H]estradiol binding was inhibited. The Scatchard plot showed a transition from a convex to a linear curve and a decrease in the Hill coefficient value from 1.61 +/- 0.02 (n = 7) in the absence of estriol or estrone to 1.04 +/- 0.04 (n = 4) in the presence of estriol and 0.99 +/- 0.03 (n = 4) in the presence of estrone. The inhibition of the positive cooperativity of [3H]estradiol binding by estriol or estrone was shown not to be due to isotope dilution of the specifically bound [3H]estradiol by the unlabeled estriol or estrone. These kinetic analyses demonstrate that the positively cooperative equilibrium binding of [3H]estradiol by the receptor, which is characteristic of the receptor's activation process, is eliminated by estriol and estrone and consistent with their partial agonist-antagonist activities observed in vivo.
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D004964:Estriol / Q000494:pharmacology*; D004970:Estrone / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium; D014599:Uterus / Q000378:metabolism*
D011960:Receptors, Estrogen; D014316:Tritium; D004970:Estrone; D004958:Estradiol; D004964:Estriol