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Cited by 330Retinoids in leukemia and cellular processesSkin Protection and AgingDermatology and Skin Diseases

Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation

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Kang, Sewon, Duell, Elizabeth A., Fisher, Gary J., Datta, Subhash C., Wang, Zeng-Quan, Reddy, Ambati P., Tavakkol, Amir, Yi, Jong Y. +3 more·1995·Journal of Investigative Dermatology
DOI 10.1111/1523-1747.ep12323445
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Abstract

We investigated the clinical, histologic, and molecular responses of normal human skin to all-trans-retinol (ROL) application, compared to those induced by topical all-trans-retinoic acid (RA), and measured ROL-derived metabolites. Up to 1.6% ROL, 0.025% RA in vehicle (70% ethanol/30% propylene glycol), or vehicle alone were applied in a double-blind fashion to normal buttock skin and occluded for 4 d. ROL produced from none to only trace erythema, which was clinically and statistically insignificant, whereas RA induced a significant 3.7-fold increase in erythema score compared to vehicle (n = 10, p < 0.01). However, ROL induced significant epidermal thickening (1.5-fold at 1.6% ROL, p < 0.01), similar to RA (1.6-fold at 0.025% RA, p < 0.01), relative to the vehicle. ROL, compared with vehicle, also increased mRNA levels of cellular retinoic acid binding protein (CRABP-II) and cellular retinol binding protein (CRBP) genes as determined by Northern analysis (5-6-fold and 6-7-fold, respectively) and riboprobe in situ hybridization. CRABP-II and CRBP protein levels were also higher following ROL than vehicle treatment, as measured by ligand binding (3.2-fold, p < 0.001; n = 7) and Western analysis (3.6-fold, p < 0.003; n = 6), respectively. Epidermal retinyl ester (RE) content, measured after removal of stratum corneum, rose 240-fold (p < 0.005, n = 5) by 24 h of ROL occlusion. RA content, however, was undetectable or detectable only at trace amounts in all samples obtained at 0, 6, 24, and 96 h after ROL occlusion. Detectability of RA was not correlated with ROL treatment (compared to untreated normal skin, p = 0.86) or baseline skin ROL levels (average r = -0.1, p > 0.3). These data demonstrate that ROL application 1) produces trace erythema not significantly different from vehicle, whereas RA causes erythema; 2) induces epidermal thickening and enhances expression of CRABP-II and CRBP mRNAs and proteins as does RA; 3) causes marked accumulation of retinyl ester; and 4) does not significantly increase RA levels. Taken together, the data are compatible with the idea that ROL may be a prohormone of RA, because it produces changes in skin similar to those produced by RA but without measurable RA or irritation.

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  • Application of all-trans-retinol on normal human skin induced epidermal thickening and increased mRNA expression of cellular retinoic acid binding protein and cellular retinol binding protein.

    “A study conducted by Kang et al. showed that the application of all-trans-retinol on normal human skin induced epidermal thickening and increased the mRNA expression of cellular retinoic acid binding protein and cellular retinol binding protein [41].”

    From Bioactive Compounds for Skin Health: A Review (2021) · cites this paper as [41]

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Authors
Kang, S., Duell, E. A., Fisher, G. J., Datta, S. C., Wang, Z.-Q., Reddy, A. P., Tavakkol, A., Yi, J. Y., Griffiths, C. E. M., Elder, J. T., & Voorhees, J. J.
Affiliations
University of Michigan (US)
ORCID
Venue
Journal of Investigative Dermatology
Publisher
Elsevier BV
Published
1995-10
Volume
105
Issue
4
Pages
549-556
ISSN
0022-202X (ISSN-L)
DOI
10.1111/1523-1747.ep12323445
OpenAlex
W2019736888
Cited by
330
References
42
Citations by year
2026: 6 · 2025: 6 · 2024: 16 · 2023: 10 · 2022: 10 · 2021: 7 · 2020: 7 · 2019: 14 · 2018: 7 · 2017: 14 · 2016: 15 · 2015: 13 · 2014: 8 · 2013: 6 · 2012: 10
FWCI
2.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Investigative Dermatology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
Keywords
all-trans-retinol, all-trans retinoic acid, epidermal hyperplasia, CRABP2, cellular retinol-binding protein, vitamin A metabolism, retinyl esters, skin irritation, erythema, topical retinoids, ligand binding, stratum corneum
MeSH terms
Administration, Cutaneous, Adult, Drug Eruptions, Dose-Response Relationship, Drug, Epidermis, Erythema, Esters, Gene Expression Regulation, Humans, Hyperplasia, Occlusive Dressings, Retinol-Binding Proteins, Safety, Tretinoin, Vitamin A, In Situ Hybridization, Receptors, Retinoic Acid, Retinol-Binding Proteins, Cellular

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