Insulin-like growth factors (IGF-I and IGF-II), IGF-binding proteins, and IGF gene expression in the offspring of ethanol-fed rats.
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.
Singh
S P
SP
Department of Medicine, Veterans Affairs Medical Center, North Chicago, IL 60064.
Srivenugopal
K S
KS
Ehmann
S
S
Yuan
X H
XH
Snyder
A K
AK
D000818:Animals; D000831:Animals, Newborn / Q000235:genetics*; D001786:Blood Glucose / Q000032:analysis; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000032:analysis / Q000097:blood / Q000235:genetics*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005317:Fetal Growth Retardation / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000235:genetics*; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008431:Maternal-Fetal Exchange; D009929:Organ Size; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013002:Somatomedins / Q000032:analysis / Q000235:genetics*
D001786:Blood Glucose; D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D013002:Somatomedins; D000431:Ethanol; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D005947:Glucose