CLASS-IV ALCOHOL RETINOL DEHYDROGENASE LOCALIZATION IN EPIDERMAL BASAL LAYER - POTENTIAL SITE OF RETINOIC ACID SYNTHESIS DURING SKIN DEVELOPMENT/

Vitamin A (retinol) plays a signaling role in the development of skin and other epithelial tissues, This is accomplished by a two-step metab olic pathway in which the rate-limiting step is oxidation of retinol t o retinal, followed by oxidation of retinal to retinoic acid, which se rves 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 fa mily has shown that class TV ADH is the most efficient isozyme for ret inol oxidation but that other isozymes can catalyze this reaction, Her e we have examined mouse skin for the expression of genes encoding cla ss I ADH and class TV 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, wher eas class IV ADH mRNA was abundant and localized in the epidermal basa l layer, providing evidence that the skin retinol dehydrogenase previo usly identified was class IV ADH, Immunohistochemical studies indicate d 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 cor nified layer. This apparent down-regulation of class IV ADH expression during keratinocyte terminal differentiation provides evidence that t he basal layer of the epidermis may be the primary site of local retin oic acid synthesis needed for retinoid signaling in the skin, (C) 1997 Wiley-Liss, Inc.