Transformation of the glucocorticoid receptor in rat liver cytosol by lysosomal enzymes.

It has previously been shown that the glucocorticoid.receptor complex in the liver cytosol undergoes limited proteolysis when incubated with trypsin or the 1,000 to 10,000 x g sediment of liver homogenate. We now show that incubation of the largest form of the dexamethasone*receptor complex, the 6.1 nm complex, with an extract of purified lysosomes from rat liver results in the formation of two smaller glucocorticoid*receptor complexes with Stokes radii of 3.6 and 1.9 nm, respectively. No other intermediate forms of the steroid.receptor complex are found after incubation with the lysosomal extract. The 6.1 nm -+ 3.6 nm + 1.9 nm complex conversion is proportional to the amount of lysosomal extract added to the incubations and occurs at a higher rate when the incubation temperature is raised. The conversion is inhibited by the addition of gelatin to the incubations but does not appear to be inhibited by any of the specific cathepsin inhibitors antipain, leupeptin, or pepstatin or by pchloromercuribenzoate. It is suggested that lysosomal protease convert the glucocorticoid *receptor complex to smaller forms, one of which lacks the capacity to bind to DNA. This mechanism may be of importance for regulation of the number of glucocorticoid *receptor complexes that reach binding sites on the chromatin, or for inactivation and breakdown of the receptor, or both.