Dynamic pattern of estradiol binding to uterine receptors of the rat. Inhibition and stimulation by unsaturated fatty acids.

The binding of estradiol to uterine cytosoluble receptors from 24-day-old rats was reduced or potentiated by unsaturated fatty acids (NEFAs), depending on the concentrations of estradiol and unsaturated NEFAs. At estradiol concentrations of up to 1.5 x 10(-8) M, unsaturated NEFAs inhibited estradiol binding to the 8 S cytosol receptor. This inhibition was dose-dependent (10-70%, p less than 0.001) and a function of NEFA unsaturation. Scatchard analysis indicated that unsaturated NEFAs caused a large decrease in receptor affinity for estradiol. Polyunsaturated NEFAs had no apparent effect on estradiol binding at estradiol concentrations of 2-4 x 10(-8) M. At high estradiol concentrations (above 4 x 10(-8) M), estradiol binding was increased 130-250% (p less than 0.01) by polyunsaturated NEFAs. This increased binding was particularly associated with proteins sedimenting at 12.5 S and the 8 S binding was, in fact, reduced. Metabolic studies showed that the reduced binding in the presence of unsaturated fatty acids was correlated with a decrease in reversibly bound estradiol at low estradiol concentrations. The increase in estradiol binding at high estradiol concentrations is the result of a reduction in reversibly bound estradiol and an increase in nonorganic solvent-extractable (water-soluble) estradiol. The amounts of these water-soluble estradiol derivatives depended on both estradiol and unsaturated NEFA concentrations. 70% of the water-soluble estradiol derivatives were trichloroacetic acid-precipitable, suggesting a covalent protein-steroid link. Thus, changes in the hydrophobic fatty acid environment of the uterine cytosol estrogen receptor could modify estrogen-receptor function by altering binding site conformation and/or by inducing changes in estradiol metabolism.