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
| Autor: | Christopher E.M. Griffiths, James T. Elder, John J. Voorhees, Elizabeth A. Duell, Jong Y. Yi, Zeng Quan Wang, Ambati P. Reddy, Gary J. Fisher, Sewon Kang, Amir Tavakkol, Subhash C. Datta |
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| Rok vydání: | 1995 |
| Předmět: |
Adult
medicine.medical_specialty Erythema Receptors Retinoic Acid Retinoic acid Tretinoin Human skin Occlusive Dressings Dermatology Administration Cutaneous Biochemistry chemistry.chemical_compound In vivo Internal medicine medicine Humans Vitamin A Molecular Biology In Situ Hybridization Hyperplasia Dose-Response Relationship Drug Chemistry Retinoid binding protein Retinol Esters Retinol-Binding Proteins Cellular Cell Biology Retinol-Binding Proteins Retinol binding protein Retinoic acid receptor Endocrinology Gene Expression Regulation Drug Eruptions Epidermis Safety medicine.symptom |
| Zdroj: | Journal of Investigative Dermatology. 105:549-556 |
| ISSN: | 0022-202X |
| Popis: | 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, p0.01). However, ROL induced significant epidermal thickening (1.5-fold at 1.6% ROL, p0.01), similar to RA (1.6-fold at 0.025% RA, p0.01), 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, p0.001; n = 7) and Western analysis (3.6-fold, p0.003; n = 6), respectively. Epidermal retinyl ester (RE) content, measured after removal of stratum corneum, rose 240-fold (p0.005, 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, p0.3). 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. |
| Databáze: | OpenAIRE |
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