Mechanism of Activation of Steroid Receptors: Involvement of Low Molecular Weight Inhibitor in Activation of Androgen, Glucocorticoid, and Estrogen Receptor Systems*

Abstract

The mechanism of activation of androgen receptor in the rat ventral prostate and glucocorticoid receptor in the rat liver was studied and compared with that of estrogen receptor in the rat uterus. Removal of low molecular weight materials from cytosol containing [³H]dihydrotestosterone-androgen receptor complexes or [³H]dexamethasone-glucocorticoid receptor complexes caused a marked increase in binding of the receptors to nuclei. Dialysis of cytosols in the absence of steroids, followed by labeling receptors with ³H-labeled steroids also enhanced nuclear binding. However, a long period (≫3 h) of dialysis of prostate or liver cytosol at 0 C in the absence of steroid also resulted in a marked decrease in steroid-binding activity, while the same treatment of the uterine cytosol caused only minimum loss of the estradiol-binding activity. Temperature-induced activation of the estrogen receptor was compared with dialysis-induced activation. Activated [³H]estradiol- receptor complexes induced by dialysis or dilution could not be further activated by warming at 25 C for 30 min. Furthermore, the dialyzable material from the liver cytosol was found to inhibit both dialysis-induced and temperature-dependent activation of uterine estrogen receptor. These results indicate that a low molecular weight material(s) regulates activation of three steroid receptor systems and may be involved in stabilization of steroid-binding activity. Temperature may induce activation of receptors by promoting dissociation of the low molecular weight inhibitor. (Endocrinology106: 1142, 1980)