Effects of glucocorticoids on the epidermal beta-adrenergic adenylate cyclase system were investigated. Long-term incubation of pig skin slices in RPMI 1640 medium resulted in the gradual decrease in the epinephrine-induced cyclic AMP accumulations of skin. The addition of hydrocortisone (100 microM) in the incubation medium prevented this decrease, and after 24- and 48-h incubation, there was a marked difference in beta-adrenergic responsiveness between control and hydrocortisone-treated skin. The study using other steroid hormones revealed that this effect on the beta-adrenergic system was relatively specific for glucocorticoids. Hydrocortisone, prednisolone, dexamethasone, and beta-methasone-17-valerate were shown to have marked effects on the beta-adrenergic system, while androstenedione, testosterone, dihydrotestosterone, progesterone, estrone, and beta-estradiol had no effect. Cortisone and estriol were shown to have similar but weaker effects than hydrocortisone. The effect of glucocorticoids was also relatively specific to the beta-adrenergic system, since there was no significant difference in adenosine-or histamine-induced cyclic AMP accumulations of skin after long-term incubation with and without hydrocortisone. The mechanism of this glucocorticoid action does not seem to be through the simple protection of the beta-adrenergic system of the skin, since the addition of hydrocortisone in the incubation medium at 24 or 48 h incubation time, when the epinephrine-induced cyclic AMP accumulation was considerably decreased, reversed the epinephrine unresponsiveness of the skin, after the additional 24-h incubation. Furthermore, the effect of hydrocortisone was inhibited by 3 different kinds of inhibitors: (a) progesterone, an inhibitor of intracytoplasmic glucocorticoid receptor binding; (b) actinomycin D, an inhibitor of messenger RNA (mRNA) synthesis; and (c) cycloheximide, an inhibitor of protein synthesis at the translation step. These results are in accordance with the view that glucocorticoids affect the beta-adrenergic system of epidermis by a mechanism requiring mRNA and protein synthesis possibly through the intracytoplasmic glucocorticoid receptor system of epidermis.
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