EXPRESSION PATTERNS OF CLASS-I AND CLASS-IV ALCOHOL-DEHYDROGENASE GENES IN DEVELOPING EPITHELIA SUGGEST A ROLE FOR ALCOHOL-DEHYDROGENASE INLOCAL RETINOIC ACID SYNTHESIS

Vitamin A (retinol) regulates embryonic development and adult epitheli al function via metabolism to retinoic acid, a pleiotrophic regulator of gene expression. Retinoic acid is synthesized locally and functions in an autocrine or paracrine fashion, but the enzymes involved remain obscure. Alcohol dehydrogenase (ADH) isozymes capable of metabolizing retinol include class I and class IV ADHs, with class III ADH unable to perform this function. ADHs also metabolize ethanol, and high level s of ethanol inhibit retinol metabolism, suggesting a possible mode of action for some of the medical complications of alcoholism. To explor e whether any ADH isozymes are linked to retinoic acid synthesis, here in we have examined the expression patterns of all known classes of AD H in mouse embryonic and adult tissues, and also measured retinoic aci d levels. Using in situ hybridization, class I ADH mRNA was localized in the embryo to the epithelia of the genitourinary tract, intestinal tract, adrenal gland, liver, conjunctival sac, epidermis, nasal epithe lium, and lung, plus in the adult to epithelia within the testis, epid idymis, uterus, kidney, intestine, adrenal cortex, and liver. Class IV ADH mRNA was localized in the embryo to the adrenal gland and nasal e pithelium, plus in the adult to the epithelia of the esophagus, stomac h, testis, epididymis, epidermis, and adrenal cortex. Class III ADH mR NA, in contrast, was present at low levels and not highly localized in the embryonic and adult tissues examined. We detected significant ret inoic acid levels in tile fetal kidney, fetal/adult intestine and adre nal gland, as well as the adult liver, lung, testis, epididymis, and u terus-all sites of class I and/or class IV ADH gene expression. These findings indicate that the expression patterns of class I ADH and clas s IV ADH, but not class III ADH, are consistent with a function in loc al retinoic acid synthesis needed for the development and maintenance of many specialized epithelial tissues.