Molecular changes associated with ethanol-induced growth suppression in the chick embryo.

In humans and in animal models the most frequently observed alcohol-related birth defect (ARBD) is intrauterine growth retardation (IUGR). The central nervous system (CNS) is sensitive to the growth inhibitory effects of in utero ethanol exposure and neonatal CNS alterations with associated behavioral deficits are a likely result of maternal ethanol consumption. Presently, little information exists as to the biochemical mechanism by which ethanol inhibits fetal CNS growth. Further, it is unknown if there are genetic differences in maternal or fetal responses to ethanol. Ongoing research using a chick model indicates that pharmacologically appropriate doses of ethanol (less than 30 mM) inhibit brain growth and reduce CNS 3',5'-cyclic adenosine monophosphate (cyclic AMP) with an associated 50% decrease in the binding of cyclic AMP by the regulatory subunit (RII) of protein kinase A. Furthermore, there is a specific loss of phosphorylation of RII by kinase catalytic subunit as a result of ethanol exposure. Because tissue cyclic AMP content and the degree of RII phosphorylation are important parameters for the regulation of protein kinase A catalytic activity, it is hypothesized that these alterations may be biochemical transformations that underlie ethanol-induced growth suppression.