Glucocorticoid Receptor Levels in Mouse Skin after Repetitive Applications of 12-O-Tetradecanoylphorbol-13-acetate and Mezerein

Female Sencar mice were given twice weekly topical applications of 0.2 ml of acetone, 4 µg of 12-O-tetradecanoylphorbol-13-acetate (TPA), 2 µg of mezerein, or 4 µg of TPA followed by 2 µg of mezerein. Whole skin cytoplasmic glucocorticoid receptor content and dissociation constants were determined at various times after the last application of the agents. After four to 12 applications of acetone, the mean glucocorticoid receptor level was 0.49 ± 0.02 pmol/mg cytosol protein, and the dissociation constant was 6.0 ± 0.17 nM. The glucocorticoid receptor level was markedly reduced and remained low for at least 72 hr after repetitive applications of TPA. The mean receptor level was 0.113 ± 0.011 (S.E.) pmol/mg cytosol protein, and the K_d was 2 to 4 times the control value. In contrast, the glucocorticoid receptor level was not significantly reduced after repetitive applications of mezerein. If four applications of mezerein were preceded by four applications of TPA, then the glucocorticoid receptor level was similar to that after TPA alone. It was also demonstrated that the glucocorticoid receptor level in papillomas was extremely low (0.022 pmol/mg cytosol protein) but was much higher in newborn skin (0.52 pmol/mg cytosol protein).