Inactivation of glucocorticoid receptors in cell-free preparations of rat liver.

We have examined the rates of inactivation of glucocorticoid receptors in cell-free preparations from several rat tissues. The t1/2 of inactivation of the glucocorticoid-binding ability of thymus, heart, and kidney cytosols (37,000 X g supernatants) ranges from 2 to 4 hr at 0 degrees, whereas that of liver is much slower (15 to 25 hr). The rate of inactivation of the glucocorticoid-binding capacity of soluble preparations from liver varies roughly according to the g force at which they have been centrifuged. The 100,000 X g supernatant. The ability of the particulate enzyme to inactivate glucocorticoid receptors at 0 degrees is not affected by protease inhibitors but is inhibited by fluoride and molybdate. The rapid inactivation of unbound glucocorticoid receptors that occurs in a high-speed (100,000 X g) supernatant preparation from rat liver at 25 degrees can be completely inhibited by molybdate. These observations suggest that the inactivation of glucocorticoid receptors observed in cell-free liver preparations in vitro is due to a nonproteolytic enzymatic function.