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We have previously reported the effect of hydrocortisone (HC) on the adenylate cyclase system of pig epidermis. HC had no effect on the basal level of cyclic AMP but there was an increased adrenaline-induced cyclic AMP accumulation when epidermal slices were incubated for more than 6 h with HC. This incubation did not alter the responsiveness to histamine. We are interested in the effects on epidermal cells of HC, which may act through the adenylate cyclase system. It is well documented that adrenaline, histamine and adenosine stimulate adenylate cyciase and cause an accumulation of cyclic AMP in pig epidermis. An increased cyclic AMP results in the inhibition of mitosis and epidermal outgrowth. Employing the rate of epidermal outgrowth and mitotic index as indicators of cyclic AMP effect, we studied the effect of HC on the adenylate cyclase system. The pretrcatment with HC (100 μM) magnified the inhibitory effect of adrenaline on epidermal outgrowth and mitosis, whereas the inhibitory effect of histamine or adenosine was not affected by HC. It is suggested that HC induced an increased responsiveness of adenylate cyclase to adrenaline, resulting in a magnified inhibitory effect of adrenaline on epidermal outgrowth and mitosis. [ABSTRACT FROM AUTHOR]