Effects of phorbol ester tumor promoters and hyperplasiogenic agents on cytoplasmic glucocorticoid receptors in epidermis.
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.
D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D003907:Dexamethasone / Q000378:metabolism; D004224:Diterpenes; D004817:Epidermis / Q000187:drug effects*; D005260:Female; D008297:Male; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology; D010704:Phorbols / Q000494:pharmacology*; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D011987:Receptors, Steroid / Q000187:drug effects*; D013696:Temperature; D013729:Terpenes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D000480:Alkynes; D002273:Carcinogens; D004224:Diterpenes; D010703:Phorbol Esters; D010704:Phorbols; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D013729:Terpenes; C015202:ethylphenylpropiolate; C011309:mezerein; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate