The role of alcohol dehydrogenase in retinoic acid homeostasis and fetal alcohol syndrome.
We previously proposed an hypothesis that fetal alcohol syndrome is caused by an ethanol-induced inhibition of retinoic acid synthesis catalyzed by alcohol dehydrogenase (ADH). Retinoic acid plays a critical role in central nervous system development which is severely disrupted in fetal alcohol syndrome. Retinoic acid is derived from retinol (vitamin A alcohol) via oxidation by retinol dehydrogenases that are members of the ADH family of isozymes, many of which also use ethanol as a substrate. We have shown that expression of the human ADH3 gene is induced by retinoic acid, thus further supporting the role of ADH in retinoic acid synthesis and suggesting the existence of a positive feedback loop. We have now extended these studies to the mouse embryo and found that it also possesses a retinoic acid-inducible ADH gene. Retinoic acid treatment was able to induce Adh-1 mRNA in 10.5-day mouse embryos and also in mouse F9 embryonal carcinoma cells. Thus, embryonic ADH can presumably be induced by retinoic acid, further strengthening the argument that ADH plays a role in embryonic retinoic acid synthesis and fetal alcohol syndrome.
Shean
M L
ML
Department of Biochemistry, Colorado State University, Fort Collins 80523, USA.
Duester
G
G
D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D046508:Culture Techniques; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008954:Models, Biological; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology
D012333:RNA, Messenger; D014212:Tretinoin; D000426:Alcohol Dehydrogenase