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 developmental and behavioral effects on the fetus; however, the specific 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 libitum, pair, and ethanol-fed rats were fed a commercial liquid diet containing either ethanol or isocaloric maltose-dextrin from day 2 of pregnancy 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 approximately 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 results 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 intrauterine and postnatal growth retardation observed in prenatally ethanol-exposed offspring.