In vitro metabolism by human skin and fibroblasts of retinol, retinal and retinoic acid

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Abstract
The metabolism of radio‐labelled retinol, retinal and retinoic acid by fresh human skin as well as by human dermal fibroblasts have been investigated in vitro. Surgically removed human skin biopsies were placed at the air‐liquid interface, and treated topically for 24 h with retinoids. At the end of the treatment period, epidermis and dermis were separated by heat. Epidermis, dermis and medium were subsequently extracted and resulting fractions were analysed by HPLC. Dermal fibroblast cultures were treated and analysed in a comparable manner. Topical application of retinoids resulted in gradient concentrations within the skin. 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 epidermis, as well as in the dermis (30 pmol to 90 pmol). In comparison, treatments 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, formed retinoic acid as well as several other metabolites (retinol esters, reduction of retinal to retinol…). Taken together, our results are consistent with an action of retinol or retinal on the skin via a retinoic acid formation and a metabolic function of the dermis.