Relationships between Mammary Estrogen Receptor and Estrogenic Sensitivity, Molecular Properties of Cytoplasmic Receptor and its Binding to Deoxyribonucleic Acid*

Abstract

The cytoplasmic estrogen receptors (ER) from mammary glands of estrogen-responsive nulliparous and estrogen-resistant lactating mice have been studied to delineate various relationships between the molecular properties of ER and estrogenic sensitivity. These studies indicate that there are essentially no differences in the hydrodynamic parameters of native ER isolated in hypotonic buffer; the ER from both tissues have a stokes radius of 80-85 .ANG., sedimentation coefficient of 9-10S, and mol wt of 300,000-340,000. However, while 60-80% of the total ER in mammary glands of nulliparous mice, upon exposure to 400 mM KCl is able to bind to DNA, under identical experimental conditions only approximately 20% of total ER from lactating mammary glands binds to DNA. Analyses of ER in buffers containing 400 mM KCl reveal that the ER in lactating mammary glands have a larger mol wt (100,000-130,000) as compared to ER in mammary glands of nulliparous mice (70,000). The ER in lactating mammary glands also appear to be more acidic when analyzed by diethylaminoethyl cellulose chromatography. Experiments performed with mixed cytosol reveal that lactating mammary cytosol contains factors which can impede the ability of ER to bind to DNA subsequent to exposure to KCl. The possible significance of the observed differences in the properties of ER from estrogen-responsive and unresponsive mammary glands has been discussed.