IN-VITRO METABOLISM BY HUMAN SKIN AND FIBROBLASTS OF RETINOL, RETINALAND RETINOIC ACID

The metabolism of radio-labelled retinol, retinal and retinoic acid by fresh human skin as well as by human dermal fibroblasts have been inv estigated in vitro. Surgically removed human skin biopsies were placed at the air-liquid interface, and treated topically for 24 h with reti noids. At the end of the treatment period, epidermis and dermis were s eparated by heat. Epidermis, dermis and medium were subsequently extra cted and resulting fractions were analysed by HPLC. Dermal fibroblast cultures were treated and analysed in a comparable manner. Topical app lication of retinoids resulted in gradient concentrations within the s kin. For each fraction, metabolites and unchanged product proportions were determined by HPLC. After treatment with retinol and retinal, low but significant amounts of retinoic acid were detected in the epiderm is, as well as in the dermis (30 pmol to 90 pmol). In comparison, trea tments with retinoic acid itself, led to higher level of retinoic acid in the epidermis and in the dermis (respectively 2050 and 420 pmol). Cultured human dermal fibroblasts, treated with retinol and retinal, f ormed retinoic acid as well as several other metabolites (retinol este rs, reduction of retinal to retinol...). Taken together, our results a re consistent with an action of retinol or retinal on the skin via a r etinoic acid formation and a metabolic function of the dermis.