EFFECT OF ETHANOL ON PLASMA AND HEPATIC INSULIN-LIKE GROWTH-FACTOR REGULATION IN PREGNANT RATS

Alcohol consumption during pregnancy has been shown to have profound d evelopmental and behavioral effects on the fetus; however, the specifi c cause of these abnormalities remains unknown. These studies examined the consequences of chronic ethanol exposure during pregnancy on the regulation of maternal plasma and hepatic insulin-like growth factors (IGFs), and their associated plasma binding proteins (IGF-BPs). Ad lib itum, pair, and ethanol-fed rats were fed a commercial liquid diet con taining either ethanol or isocaloric maltose-dextrin from day 2 of pre gnancy through parturition and killed 6 hr postpartum. Maternal plasma IGF-1 concentrations were reduced 51% in ethanol, compared with pair- fed mothers, with a corresponding 20% reduction in hepatic IGF-1 mRNA levels. In contrast, plasma IGF-2 concentrations were increased simila r to 100% in ethanol-fed mothers. Whereas the smaller forms of the IGF -binding protein subunits (24 kDa and 32-29 kDa) were not affected by ethanol treatment, a significant reduction was observed in the binding subunit of IGF-BP3 (45-40 kDa) in ethanol-exposed mothers. These resu lts suggest that alterations in plasma and hepatic IGF regulation may contribute to changes in maternal and placental metabolism and hormone regulation during pregnancy, which may in turn contribute to the intr auterine and postnatal growth retardation observed in prenatally ethan ol-exposed offspring.