Dermal fibroblasts actively metabolize retinoic acid but not retinol

The accessibility of plasma retinol and retinoic acid to the epidermis may be influenced by the number and metabolic capacity of fibroblasts in papillary dermis. The metabolism of retinol-binding protein-bound all-trans-retinol, and albumin-bound all-trans-retinoic acid, by fibroblasts cultured on plastic dishes or in type I collagen gels, was examined. There were no significant differences in the metabolism of either retinoid by fibroblasts as a function of culture condition. There were large differences between retinoids, however. Retinoic acid was rapidly taken up and metabolized to unidentified polar metabolites that were released to the medium. Metabolic capacity was not saturated up to a medium retinoic acid concentration of 1 microM, and was induced further by prior exposure to retinoic acid. In contrast, retinol, although readily taken up, was not metabolized, i.e., neither retinoic acid nor retinyl ester was formed. By immunohistochemistry, the average number of fibroblasts in a 100 microm thickness of papillary dermis was estimated to be 1 x 10(6) cells per cm2. Utilizing this value, the capacity of dermal fibroblasts to metabolize retinoic acid based on fibroblast abundance in the dermis was calculated. The results suggest that fibroblasts could limit delivery of plasma retinoic acid but not retinol to the epidermis on the basis of their metabolic capacity and abundance in the dermis.