INHIBITION OF THE GLUCOCORTICOID RECEPTOR EXPRESSION BY DIVERSE TUMORPROMOTERS IN SENCAR MOUSE EPIDERMIS

Glucocorticoid hormones are very potent inhibitors of keratinocyte pro liferation. Their function is mediated by the glucocorticoid receptor (GR) which is highly expressed in mouse epidermis. In the study report ed here we compared the effect of 12-O-tetradecanoyl-phorbol-13-acetat e (TPA) and non-phorbol ester tumor promoters such as okadaic acid, ch rysarobin, and benzoyl peroxide on the levels of GR protein and mRNA i n SENCAR mouse epidermis. Glucocorticoid binding assay and Northern bl ot analysis revealed that all four tumor promoters decreased both GR p rotein and mRNA levels in keratinocytes in vivo. We also found that TP A and okadaic acid inhibited GR expression in keratinocyte cell line. These results suggest that GR inhibition may play an important role in mouse skin hyperplasia and promotion of skin carcinogenesis.