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

Elizabeth A. Duell, Fadila Derguini, Sewon Kang, James T. Elder, John J. Voorhees

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)178-182
Number of pages5
JournalJournal of Investigative Dermatology
Issue number2
StatePublished - 1996
Externally publishedYes


  • Didehydroretinol
  • Metabolism
  • Pharmacology
  • Retinyl glucuronides

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology


Dive into the research topics of 'Extraction of human epidermis treated with retinol yields retro-retinoids in addition to free retinol and retinyl esters'. Together they form a unique fingerprint.

Cite this