The estriol-induced inhibition of the estrogen receptor's positive cooperativity

The effect of estriol on the positive cooperativity of [3H]estradiol binding to the partially purified calf uterine estrogen receptor was investigated using the kinetic analysis of Sasson and Notides (J. biol. Chem. 257 1982, 11540). The receptor was titrated with variable concentrations of [3H]estradiol with or without estriol; the estriol was maintained in a constant molar ratio to the [3H]estradiol concentration. A 4-fold molar excess of estriol above the [3H]estradiol concentrations inhibited the receptor's cooperative [3H]estradiol binding. In the absence of estriol, the [3H]estradiol receptor interaction was highly cooperative, the Scatchard plot was convex and the Hill coefficient was 1.61 +/- 0.02. In the presence of sufficient estriol to reduce the maximally bound [3H]estradiol to 77%, the Scatchard plot was linear and the Hill coefficient was 1.04 +/- 0.04. The inhibition of the cooperative [3H]estradiol binding by estriol was not due to isotope dilution of the specifically bound [3H]estradiol by the unlabeled estriol. These data demonstrate that the cooperative binding of [3H]estradiol by the receptor that is characteristic of the equilibrium between the two states of the receptor (active and nonactive) is eliminated by the presence of estriol. This finding is consistent with the agonist/antagonist activity of estriol observed in vivo.