A novel short-chain alcohol dehydrogenase from rats with retinol dehydrogenase activity, cyclically expressed in uterine epithelium.
Retinoic acid is necessary for the maintenance of many lining epithelia of the body, such as the epithelium of the luminal surface of the uterus. Administration of estrogen to prepubertal rats induces in these epithelial cells the ability to synthesize retinoic acid from retinol, coincident with the appearance of cellular retinoic acid-binding protein, type two, which is normally present in these cells only at estrus in the mature, cycling animal. Here, we report the isolation, from a cDNA library prepared from uterine mRNA collected at the estrous stage and from a rat mammary adenocarcinoma cell line, of a cDNA that encodes a novel retinol dehydrogenase. A member of the short-chain alcohol dehydrogenase family, the encoded enzyme was capable of metabolizing retinol to retinal when expressed in cells after transfection of its cDNA. When cotransfected with the cDNA of human aldehyde 6, a known retinaldehyde dehydrogenase, the transfected cells synthesized retinoic acid from retinol. Immunohistochemical analysis revealed that the protein was present in the uterine lining epithelium of the mature animal only at estrus, coincident with the presence of cellular retinol-binding protein and cellular retinoic acid-binding protein, type two. Consequently, this novel short-chain alcohol dehydrogenase is an excellent candidate for the retinol dehydrogenase that catalyzes the first step in retinoic acid biosynthesis that occurs in uterine epithelial cells.
Rexer
Brent N
BN
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Ong
David E
DE
D000230:Adenocarcinoma / Q000201:enzymology; D000426:Alcohol Dehydrogenase / Q000235:genetics* / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D000072467:Cytochrome P450 Family 2; D004848:Epithelium / Q000201:enzymology*; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism; D014599:Uterus / Q000201:enzymology*; D014801:Vitamin A / Q000378:metabolism
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C082928:retinoic acid binding protein II, cellular; D014801:Vitamin A; D014212:Tretinoin; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; C022520:retinol dehydrogenase; C504568:Cyp2d1 protein, rat; D000072467:Cytochrome P450 Family 2; D000444:Aldehyde Dehydrogenase