Shean M L, Duester G
Department of Biochemistry, Colorado State University, Fort Collins 80523, USA.
Alcohol Alcohol Suppl. 1993;2:51-6.
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.
我们先前提出了一个假说，即胎儿酒精综合征是由乙醇诱导的对酒精脱氢酶（ADH）催化的视黄酸合成的抑制作用所引起的。视黄酸在中枢神经系统发育中起着关键作用，而在胎儿酒精综合征中该发育过程会受到严重破坏。视黄酸是通过视黄醇脱氢酶氧化视黄醇（维生素A醇）而产生的，视黄醇脱氢酶是ADH同工酶家族的成员，其中许多成员也将乙醇用作底物。我们已经表明，人ADH3基因的表达是由视黄酸诱导的，从而进一步支持了ADH在视黄酸合成中的作用，并提示存在一个正反馈环。我们现在已将这些研究扩展到小鼠胚胎，发现其也拥有一个视黄酸诱导型ADH基因。视黄酸处理能够在10.5天的小鼠胚胎以及小鼠F9胚胎癌细胞中诱导Adh-1 mRNA。因此，胚胎ADH大概可以由视黄酸诱导，这进一步强化了ADH在胚胎视黄酸合成和胎儿酒精综合征中起作用的观点。
