Inhibition of glucocorticosteroid action in cultured L-929 mouse fibroblasts by RU 486, a new anti-glucocorticosteroid of high affinity for the glucocorticosteroid receptor.

The rate of growth of L-929 mouse fibroblasts in vitro is decreased by the glucocorticosteroid dexamethasone (dex) in vitro, as well as cell adhesiveness. These effects were abolished by RU 486, a new synthetic anti-hormone steroid, in both serum-containing medium and serum-free, chemically defined culture medium. RU 486 did not display any glucocorticosteroid-like activity. 3H-RU 486 binds with high affinity (KDeq approximately 0.4 nM) to the same high affinity receptor-binding sites as dex (KD approximately 0.5 nM) in the cell cytosol, as indicated by Scatchard plot, gradient-ultracentrifugation and competition studies. After incubation of whole cells with 3H-RU 486 at 37 degrees C, a radioactive antihormone-receptor complex was found in the nucleus. However, quantitative studies vs 3H-dex indicated that the antagonist provokes less nuclear receptor complex than the agonist.