Sandstrom L P, Sandstrom P A, Pennington S N
Department of Biochemistry, East Carolina University, School of Medicine, Greenville, NC 27834.
Alcohol. 1993 Jul-Aug;10(4):303-10. doi: 10.1016/0741-8329(93)90010-l.
In utero exposure to ethanol is associated with significant increases in fetal morbidity and mortality as well as with behavioral and learning problems that appear later in life. Growth suppression of the developing child is the most frequent physical effect of ethanol exposure and is correlated with specific molecular changes within the developing organism. The present report suggests that embryonic ethanol exposure suppresses the normal developmental increase in ornithine decarboxylase (ODC) activity. The loss of ODC activity during the early stages of development is dose-dependent and is correlated with the degree of growth suppression. Because ODC is the rate-limiting step for the synthesis of the polyamines and thus appears to be a focal enzyme for the regulation of growth, we have investigated the biochemical consequences of an ethanol-induced inhibition of ODC activity. Using intact chick embryos as well as cultured embryonic tissue, these studies indicate that ethanol-induced changes in tissue putrescine content result in growth suppression because a single dose of exogenous putrescine blocked the growth suppression. In cultured tissue, ethanol exposure inhibited the ability of a known trophic factor (insulin) to induce ODC activity. The loss of insulin-inducible decarboxylase activity as a result of ethanol exposure was specific to ODC, but ethanol per se had no effect on ODC activity in vitro. The data suggest that exposure to ethanol results in a resistance of the embryonic tissue to the action of insulin and thereby disrupts the molecular path by which this mitogenic compound induces the expression of ODC enzymatic activity.
子宫内暴露于乙醇与胎儿发病率和死亡率的显著增加以及生命后期出现的行为和学习问题相关。发育中儿童的生长抑制是乙醇暴露最常见的身体影响，并且与发育中生物体的特定分子变化相关。本报告表明，胚胎期乙醇暴露会抑制鸟氨酸脱羧酶（ODC）活性在正常发育过程中的增加。发育早期ODC活性的丧失是剂量依赖性的，并且与生长抑制程度相关。由于ODC是多胺合成的限速步骤，因此似乎是生长调节的关键酶，我们研究了乙醇诱导的ODC活性抑制的生化后果。使用完整的鸡胚以及培养的胚胎组织，这些研究表明，乙醇诱导的组织腐胺含量变化导致生长抑制，因为单剂量的外源性腐胺可阻止生长抑制。在培养的组织中，乙醇暴露抑制了已知营养因子（胰岛素）诱导ODC活性的能力。乙醇暴露导致的胰岛素诱导的脱羧酶活性丧失对ODC具有特异性，但乙醇本身在体外对ODC活性没有影响。数据表明，暴露于乙醇会导致胚胎组织对胰岛素的作用产生抗性，从而破坏这种有丝分裂化合物诱导ODC酶活性表达的分子途径。
