EFFECTS OF GLUCOCORTICOIDS ON THE BETA-ADRENERGIC ADENYLATE-CYCLASE SYSTEM OF PIG SKIN

[摘要] 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 cAMP accumulations of skin. The addition of hydrocortisone (100 .mu.M) 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 had marked effects on the .beta.-adrenergic system, while androstenedione, testosterone, dihydrotestosterone, progesterone, estrone and .beta.-estradiol had no effect. Cortisone and estriol had similar but weaker effects than hydrocortisone. The effect of glucocorticoids was also relatively specific to the .beta.-adrenergic systm, since there was no significant difference in adenosine-or histamine-induced cAMP 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 cAMP accumulation was considerably decreased, reversed the epinephrine unresponsiveness of the skin, after the additional 24-h incubation. The effect of hydrocortisone was inhibited by 3 different kinds of inhibitors: progesterone, an inhibitor of intracytoplasmic glucocorticoid receptor binding; actinomycin D, an inhibitor of protein synthesis at the translation step.