Human skin retinoid-binding proteins and therapy with synthetic retinoids: a still unexplained link

Human skin contains several proteins that could bind retinoids. One is the retinol-binding protein (RBP, the plasma carrier of natural vitamin A, retinol, which was found to also bind retinoic acid (RA) in vitro. A polyacrylamide gel electrophoresis technique followed by protein immunoblot analysis with an antiserum specific against RBP was developed. This technique allowed us to study the binding of several natural and synthetic retinoids to the plasma RBP; it was found that only natural retinoids bind to RBP in vitro; RA binding was found to induce major conformational changes in the protein. The technique was then used for the study of RBP in human epidermal and dermal extracts; this showed that RBP degradation with loss of binding properties for retinol occurred within the epidermis. A polyacrylamide gel electrophoresis binding assay was developed for studying cellular retinol-(CRABP) and retinoic acid-(CRABP) binding protein in human skin cytosolic extracts. CRABP was (1) found at much higher levels in normal epidermis than in the dermis (2); dramatically elevated in psoriatic plaques and in some retinoid-responsive dermatoses, and (3) up-modulated by both topical and systemic administration of natural and synthetic retinoids. Such alterations were not observed for CRBP. From these and other observations presented here, it appears that CRABP should be one of the first candidates to be carefully analyzed in the search of the cellular receptor for the mediation of the synthetic retinoids pharmacological effects.