Ethanol-induced insulin resistance suppresses the expression of embryonic ornithine decarboxylase activity.
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.
Department of Biochemistry, East Carolina University, School of Medicine, Greenville, NC 27834.
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Sandstrom
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Sandstrom
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Pennington
D000818:Animals; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D007333:Insulin Resistance; D065108:Ornithine Decarboxylase Inhibitors; D011700:Putrescine / Q000378:metabolism / Q000494:pharmacology
D065108:Ornithine Decarboxylase Inhibitors; D000431:Ethanol; D011700:Putrescine; D000518:Eflornithine