Extraction of Human Epidermis Treated with Retinol Yields Retro-Retinoids in Addition to Free Retinol and Retinyl Esters

• Published in: Journal of investigative dermatology Vol. 107; no. 2; pp. 178 - 182
• Main Authors: Duell, Elizabeth A., Kang, Sewon, Elder, James T., Voorhees, John J., Derguini, Fadila
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.1996
• Subjects: Adult; Chromatography, High Pressure Liquid; didehydroretinol; Epidermis - chemistry; Epidermis - drug effects; Epidermis - metabolism; Esters - metabolism; Humans; metabolism; pharmacology; Retinoids - metabolism; retinyl glucuronides; Stereoisomerism; Tissue Extracts - chemistry; Vitamin A - analogs & derivatives; Vitamin A - analysis; Vitamin A - metabolism; Vitamin A - pharmacology; didehydroretinol; metabolism; retinyl glucuronides; pharmacology
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1111/1523-1747.ep12329576

Vitamin A, all-trans-retinol, is metabolized to retinoic acid in vivo by a tightly controlled two-step conversion. Retinoic acid then binds to nuclear receptors and modulates cellular proliferation and differentiation. Because only a small fraction of retinol applied topically can be metabolized to retinoic acid, alternative pathways of retinol metabolism in skin were investigated. Retinol (0.4%) was applied to adult human skin under occlusion for 6h to 4 d. The conversion of retinal into various metabolites such as 14-hydroxy-4,14-retro-retinol, anhydroretinol, 4-oxoretinol, retinyl esters, and retinyl glucuronides was investigated. The level of 14-hydroxy-retro-retinol was increased from undetectable at time 0 to 326ng/g wet weight of tissue at 6h (6% of the retinol level) and maintained approximately the same concentration at 24h to 409ng/g wet weight (1.9% of the retinol level); it decreased to 48ng/g wet weight of tissue (12% of its maximum level) by 4 d. Anhydroretinol was undetectable at time 0, increased only slightly at 6 h, and remained at the same level. We did not detect 4-oxoretinol. Because 14-hydroxy-retro-retinol was found in the retinol-treated areas, its effects on epidermis were compared with those of retinol. Topical application of trans-retinol (0.3%) significantly increased both epidermal thickness and cellular retinoic acid binding protein II mRNA, whereas 14-hydroxy-4,14-retro-retinol (0.3%) did not increase either of these well-characterized cutaneous retinoid responses. Retinol, when applied topically in pharmacologic doses to human epidermis, remained as free retinol, was metabolized primarily to retinol ester, and was metabolized to a lesser extent to retro-retinoids and didehydroretinol.