Extraction of human epidermis treated with retinol yields retro-retinoids in addition to free retinol and retinyl esters Journal Article


Authors: Duell, E. A.; Derguini, F.; Kang, S.; Elder, J. T.; Voorhees, J. J.
Article Title: Extraction of human epidermis treated with retinol yields retro-retinoids in addition to free retinol and retinyl esters
Abstract: 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 6 h to 4 d. The conversion of retinol into various metabolites such as 14-hydroxy-4,14-retro-retinol, anhydroretinol, 4-oxo-retinol, retinyl esters, and retinyl glucuronides was investigated. The level of 14-hydroxy-retro-retinol was increased from undetectable at time 0 to 326 ng/g wet weight of tissue at 6 h (6% of the retinol level) and maintained approximately the same concentration at 24 h to 409 ng/g wet weight (1.9% of the retinol level); it decreased to 48 ng/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-oxo-retinol. 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.
Keywords: adolescent; controlled study; human tissue; cell proliferation; metabolism; epidermis; cell differentiation; drug metabolism; retinol; retinoid; normal human; pharmacology; human experiment; topical drug administration; human; priority journal; article; retinoic acid binding protein; didehydroretinol; retinyl glucuronides; retinol ester
Journal Title: Journal of Investigative Dermatology
Volume: 107
Issue: 2
ISSN: 0022-202X
Publisher: Elsevier Science, Inc.  
Date Published: 1996-08-01
Start Page: 178
End Page: 182
Language: English
DOI: 10.1111/1523-1747.ep12329576
PUBMED: 8757759
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 22 November 2017 -- Source: Scopus
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