RU 486 stabilizes the glucocorticoid receptor in a non-transformed high molecular weight form in intact thymus cells under physiological conditions.

When incubated at 37 degrees C for 1 h with intact rat thymocytes [3H]RU 486 underwent only partial nuclear transfer since more than 65% of the receptor bound radioactivity was still cytosolic (versus less than 10% for [3H]triamcinolone acetonide). Moreover when prepared and assayed in physiological buffers, i.e. physiological ionic strength and absence of molybdate, the cytosolic [3H]RU 486-receptor complex displayed a 7-8 nm Stokes radius after analysis by high performance size exclusion chromatography. This high size complex appeared stable for more than 24 h in the native cytosol. However its apparent sedimentation constant was 4S after sucrose gradient centrifugation for 16 h in the same buffer. These results suggested that RU 486 stabilizes a high molecular weight form of the receptor in intact cells and that this form dissociates during sucrose gradient analysis. The conditions of this in vitro dissociation were examined and compared with the results of a kinetic study of the nuclear transfer of [3H]RU 486. [3H]Triamcinolone acetonide was used as reference glucocorticoid agonist.