TY - JOUR
T1 - Effects of phorbol ester tumor promoters and hyperplasiogenic agents on cytoplasmic glucocorticoid receptors in epidermis
AU - Davidson, K. A.
AU - Slaga, T. J.
N1 - Funding Information:
Glucocorticoid (GC) hormones have varied physiologic and biochemical effects in target tissues [1]. They are known to be potent inhibitors of DNA synthesis and cell proliferation in lymphoid cells [2], fibroblasts [3], and skin [4-6]. GCs, both natUJ'aJ and synthetic, inhibit mouse skin carcinogenesis and tumor promotion induced by 12-0-tetradecanoylphorbol-13-acetate (TPA) [6-10]. One of their major effects on tumor promotion is the inhibition of TP A-induced epidermal hyperplasia and inflammation [6,10,11]. Not only do exogenous GCs influence skin tumor promotion, but endogenous GCs appeal' to influence tumo.!: promotion as well. Train in [8] observed that adrenalectomy enhances tumor promotion induced by croton oil. The response of a target tissue to steroid hormones is initiated by binding of steroid hormones to specific cytoplasmic receptors, followed by translocation of steroid-hormone receptor complexes to the nucleus, where they bind to acceptor sites on Manuscript received October 19, 1981; accepted for publication April 6, 1982. By acceptance of' this article, the publisher or recipient acknowledges the right of the U. S. Government to retain a nonexclusive, royalty-free license in and to any copyright covering the article. This research was sponsored by the Office of Health and Environmental Research, U.S. Department of Energy, under cont1'8ct W-7405-eng-26 with the Union Carbide Corporation. Reprint requests to: Dr. K. A. Davidson, Biology Division, Oak Ridge National Laboratory, P.O. Box Y, Oak Ridge, Tennessee 37830. Abbreviations: Dex: dexamethasone - EPP: ethylphenylpropiolate GC: glucocorticoid TPA: 12-0-tetradecanoylphorbol-13-acetate chromatin, thus stimulating genetic transcription [12]. The purpose of this investigation was to determine whether a GC binding component (receptor) was present in adult mouse epidermis through which exogenous GCs may act to inhibit tumor promotion and through which endogenous hormones may prevent a maximum response. We also determined whether TPA and other hyperplasiogenic agents had an effect on the level of epidermal cytosol GC receptor. In this paper evidence is provided to support the hypotheses that GC receptors are present in epidermal cells and that the number of receptors may be important in epidermal cell proliferation.
PY - 1982
Y1 - 1982
N2 - 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 μg) 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.
AB - 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 μg) 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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U2 - 10.1111/1523-1747.ep12529883
DO - 10.1111/1523-1747.ep12529883
M3 - Article
C2 - 7142739
AN - SCOPUS:0020427103
VL - 79
SP - 378
EP - 382
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 6
ER -