Singh S P, Srivenugopal K S, Ehmann S, Yuan X H, Snyder A K
Department of Medicine, Veterans Affairs Medical Center, North Chicago, IL 60064.
J Lab Clin Med. 1994 Aug;124(2):183-92.
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.
胰岛素样生长因子I和II（IGF-I、IGF-II）以及IGF结合蛋白（IGBP）是胎儿生长的重要调节因子。胎儿生长受限是胎儿酒精综合征的主要组成部分，该综合征与母亲酗酒有关。本研究探讨了妊娠期间喂食等热量流质饮食的大鼠（AF，自由采食对照组；PF，配对喂食对照组；EF，乙醇喂食组）胎儿中IGF系统成分与乙醇诱导的生长受限之间的关系。测定了胎儿肝脏中IGF-I和IGF-II的基因表达以及血清和肝脏中IGF和IGBP的浓度。EF组胎儿的平均体重分别比PF组和AF组后代轻13%和16%（p<0.01）。与PF组和AF组胎儿相比，EF组胎儿血清IGF-I浓度降低了17%和22%（p<0.05）。胎儿体重与胎儿血清IGF-I、IGF-II呈正相关（r分别为0.566，p<0.01和0.412，p<0.05）。胎儿肝脏重量与胎儿肝脏IGF-I和IGF-II相关，r值分别为0.514（p<0.01）和0.493（p<0.01）。与PF组和AF组后代相比，EF组肝脏IGF-II mRNA丰度降低了27%和26%（p<0.05）。胎儿肝脏IGF-I mRNA表达水平较低，但在EF组幼崽中也有类似程度的降低。EF组胎儿血清中IGBP含量增加（与AF组相比，p<0.05），且与胎儿体重呈负相关（r=-0.505，p<0.01）。IGF-I和IGF-II基因表达减少、组织和循环肽水平降低，以及血清IGBP丰度的相反变化，可能在胎儿酒精综合征的发病机制中起作用。
