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  • Title: Effects of phorbol ester tumor promoters and hyperplasiogenic agents on cytoplasmic glucocorticoid receptors in epidermis.
    Author: Davidson KA, Slaga TJ.
    Journal: J Invest Dermatol; 1982 Dec; 79(6):378-82. PubMed ID: 7142739.
    Abstract:
    Glucocorticoids (anti-inflammatory steroids) are very potent inhibitors of mouse skin tumor promotion induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). This report describes a high-affinity, limited-capacity binding component which specifically interacts with glucocorticoids and which is identified as a glucocorticoid (GC) receptor present in the cytosol of adult mouse epidermis. Also described is the effect of a single application of TPA and other hyperplasiogenic agents on the level of epidermal cytosol GC receptor. After treatment with acetone the epidermal GC receptor level was 0.38 pmol/mg cytosol protein, whereas after application of TPA (4 micrograms) there was a time-dependent transient decrease in the level of GC receptor (39% of control 24 hr after TPA) followed by an increase (55% and 66% of control 48 and 72 hr, respectively, after TPA). Hyperplasiogenic agents such as mezerein and ethylphenylpropiolate were also effective in causing a reduction in the level of epidermal cytosol GC receptor level, but weak tumor promoters such as phorbol dibenzoate and 4-O-methyl TPA were less effective than TPA. Therefore, there is a good correlation among agents which induce epidermal hyperplasia and agents which cause a reduction in epidermal cytosol GC receptor levels. The functional significance of the decrease in receptor level is discussed.
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