Insulin-like growth factors (IGF-I and IGF-II), IGF-binding proteins, and IGF gene expression in the offspring of ethanol-fed rats

Abstract

Insulin-like growth factors I and II (IGF-I, IGF-II) and IGF-binding proteins (IGBPs) are important modulators of fetal growth. Fetal growth retardation is a major component of the fetal alcohol syndrome, which is associated with maternal alcoholism. This study examined the relationship of IGF-system components to growth retardation induced by ethanol in fetuses of rats fed equicaloric liquid diets (AF, ad libitum-fed controls; PF, pair-fed controls; EF, ethanol-fed) during gestation. The gene expression of IGF-I and IGF-II in fetal liver and the concentration of IGFs and IGFBPs in serum and liver were determined. The mean weight of EF fetuses was 13% and 16% less (p < 0.01) than that of PF and AF offspring, respectively. The serum concentration of IGF-I was decreased (p < 0.05) by 17% and 22% in EF as compared with PF and AF fetuses. Fetal body weight showed positive correlations with fetal serum IGF-I IGF-II (r = 0.566, p < 0.01, and r = 0.412, p < 0.05, respectively) Fetal liver weight correlated with fetal liver IGF-I and IGF-II, with r values of 0.514 (p < 0.01) and 0.493 (p < 0.01). Hepatic IGF-II mRNA abundance was decreased (p < 0.05) by 27% and 26% in EF as compared with PF and AF offspring. The level of fetal liver IGF-I mRNA expression was low but was also reduced comparably in EF pups. IGFBP content in EF fetal serum was increased (p < 0.05 vs AF), and correlated negatively with fetal body weight (r = -0.505, p < 0.01). The diminished IGF-I and IGF-II gene expression and the reduced tissue and circulating peptide levels, along with a converse change in serum IGFBP abundance, may have a role in the pathogenesis of fetal alcohol syndrome.