Effect of Hydrocortisone Aceponate on Proliferation, Total Protein Synthesis and Collagen Synthesis in Human skin Fibroblasts in vitro. Hydrocortisone aceponate, a new topical hydrocortisone derivative with esterification in positions 17 and 21, inhibits the incorporation of 3H-thymidine in DNA in human skin fibroblasts less strongly than the halogenated glucocorticosteroids betamethasone-17-valerate and clobetasol-17-propionate. Prednicarbate, a prednisolone derivative esterified in positions 17 and 21, possesses antiproliferative properties which are stronger than those of hydrocortisone aceponate, but weaker than those of the halogenated corticosteroids. The glucocorticosteroid effect on total protein and collagen synthesis of skin fibroblasts was determined by measurement of amino acid incorporation. In logarithmically growing cultures, the total protein synthesis rate was stimulated by low corticosteroid concentrations and inhibited by high concentrations. The strongest inhibition was obtained with halogenated glucocorticosteroids. In confluent, non-proliferative cell cultures, all glucocorticosteroids had a stimulating effect on total protein and collagen synthesis. Hydrocortisone aceponate and prednicarbate had a more favourable effect on collagen synthesis than the two halogenated glucocorticosteroid derivatives. According to these results, halogenation and the insertion of double bonds in the steroidal skeleton lead more readily to anti-proliferative effects than esterification in positions 17 and 21.