Effect of Molybdate on Activation and Stabilization of Steroid Receptors*

Abstract

The effects of molybdate on activation and stability of glucocorticoid, androgen, and estrogen receptors were studied. The activation of steroid receptors by heating or dialysis was inhibited by molybdate, but molybdate had no effect on the nuclear binding of previously activated steroid-receptor complexes. The inhibitory effect of molybdate on activation was concentration dependent and was reversed when molybdate wasremoved by dialysis or gel filtration on Sephadex G-25. The steroid-binding capacities of the unoccupied glucocorticoid and androgen receptors were markedly reduced by removal of a small molecular weight factor(s) from the cytosol by dialysis or gel filtration on Sephadex G-25, even at 0 C. Molybdate blocked both this loss of steroid-binding ability on dialysis and also the heat-induced destabilization of the receptors. The dialysateof rat liver cytosol and molybdate had synergistic effects in increasing the stability of the glucocorticoid receptor in the cytosol after gel filtration at 25 These findings suggest that activation and destabilization have a common mechanism which involves a small molecular weight component(s) and that molybdate has a specific inhibitory effect on this mechanism.