title: Class IV alcohol/retinol dehydrogenase localization in epidermal basal layer: potential site of retinoic acid synthesis during skin development.
abstract: Vitamin A (retinol) plays a signaling role in the development of skin and other epithelial tissues. This is accomplished by a two-step metabolic pathway in which the rate-limiting step is oxidation of retinol to retinal, followed by oxidation of retinal to retinoic acid, which serves as the active ligand to activate nuclear retinoic acid receptors. Previous studies in mouse skin have shown that retinol oxidation is catalyzed by a cytosolic retinol dehydrogenase that may be a member of the alcohol dehydrogenase (ADH) enzyme family. Analysis of the ADH family has shown that class IV ADH is the most efficient isozyme for retinol oxidation but that other isozymes can catalyze this reaction. Here we have examined mouse skin for the expression of genes encoding class I ADH and class IV ADH, the only ADH isozymes in this species able to function as retinol dehydrogenases in vitro. In situ hybridization analysis of mouse skin revealed that class I ADH mRNA was absent, whereas class IV ADH mRNA was abundant and localized in the epidermal basal layer, providing evidence that the skin retinol dehydrogenase previously identified was class IV ADH. Immunohistochemical studies indicated that class I ADH protein was absent in the mouse skin, but class IV ADH protein was detected primarily in the basal layer of the epidermis, with less detection in the spinous layer and no detection in the cornified layer. This apparent down-regulation of class IV ADH expression during keratinocyte terminal differentiation provides evidence that the basal layer of the epidermis may be the primary site of local retinoic acid synthesis needed for retinoid signaling in the skin.
authors.affiliation: Burnham Institute, La Jolla, California 92037, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Haselbeck
authors.forename: H L
authors.initials: HL
authors.lastname: Ang
authors.forename: G
authors.initials: G
authors.lastname: Duester
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004817:Epidermis / Q000201:enzymology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D012867:Skin / Q000201:enzymology* / Q000254:growth & development; D014212:Tretinoin / Q000378:metabolism
chemical_list: D014212:Tretinoin; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; C105552:alcohol dehydrogenase IV; C022520:retinol dehydrogenase