Nuclear concentration of estriol in superfused human endometrium; competition with estradiol

Human endometrial slices were superfused with tritiated estriol (E₃). No metabolism of E₃ was noted. The ratio of concentrations of the hormone in tissue and superfusion medium (T/M)_E3 was found to be approximately 4. When the concentrations of [³H]-E₃ in the medium were increased from 18 to 700 ng/ml. the intracellular concentrations of E₃ were proportionally elevated. However, the level of E₃ tightly bound to nuclei reached a maximum value. This value was equivalent to the saturation level of nuclear bound estradiol (E₂) obtained when another portion of the same tissue was superfused with excess E₂. Competition of E₃ and E₂ for nuclear binding was observed when tissue slices were superfused with mixtures of the two tritiated steroids. The nuclear E₂ displaced was stoichiometrically replaced by E₃, likely as a result of competition for the same binding sites of the receptor in the nucleus. A 50% displacement of E₂ from the receptor in the nucleus was achieved when the ratio of intracellular concentrations of E₃ and E₂ was about 2. Calculations are presented to show that this ratio corresponds to the relative association constants of the E₂- and E₃-receptor complexes in the nucleus.