title: Expression of the genes for insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding proteins-1 and -2 in fetal rat under conditions of intrauterine growth retardation caused by maternal fasting.
abstract: Evidence suggests that insulin-like growth factors-I and -II (IGF-I and II) play a role in regulating fetal growth and development. In the fetus, IGF-I and -II are complexed with two specific binding proteins (IGFBP-1 and -2), which are thought to modulate the actions of the IGFs in target tissues. We examined regulation of the genes for IGF-I, IGF-II, IGFBP-1, and IGFBP-2 in fetal rat liver in an experimental model for intrauterine growth retardation caused by maternal fasting on days 17-21 of gestation. The mean weight of fetuses from the fasted dams was 27-32% lower than the mean weight of fetuses from the fed dams. The concentration of immunoreactive IGF-I was decreased by 71% in serum of fetuses from the fasting dams. The concentration of immunoreactive IGF-II was slightly decreased (by 12%) in serum of fetuses from the fasting dams, whereas the concentration of immunoreactive pro-IGF-II E-domain peptide was decreased by 31%. The abundance of hepatic IGF-I mRNA was decreased by 55% in fetuses from the fasting dams. In contrast, the abundance of IGF-II mRNA in fetal liver was not significantly decreased by maternal fasting. Maternal fasting caused a 2-fold increase in the abundance of IGFBP-1 mRNA in fetal liver, whereas it did not change the abundance of IGFBP-2 mRNA. The induction of IGFBP-1 mRNA in liver of the growth-retarded fetuses is similar to the induction that occurs in liver of fasting adults, while the lack of regulation of IGFBP-2 mRNA differs from the strong induction of IGFBP-2 mRNA that occurs in liver of fasting adults. In summary, these results indicate that maternal fasting causes a decrease in fetal IGF-I gene expression, a decrease in fetal serum IGF-I, and a slight decrease in fetal serum IGF-II and pro-IGF-II E-domain peptide concentrations. Maternal fasting also causes an increase in fetal IGFBP-1 gene expression. Changes in fetal insulin and glucose may be related to changes in expression of the IGF-I and IGFBP-1 genes in the growth-retarded fetuses. The decreased expression of IGF-I and -II and increased expression of the IGFBP-1 gene may contribute to the fetal growth retardation observed in this model system.
authors.affiliation: Molecular, Cellular, and Nutritional Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: D S
authors.initials: DS
authors.lastname: Straus
authors.forename: G T
authors.initials: GT
authors.lastname: Ooi
authors.forename: C C
authors.initials: CC
authors.lastname: Orlowski
authors.forename: M M
authors.initials: MM
authors.lastname: Rechler
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D005215:Fasting; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000503:physiopathology*; D005333:Fetus / Q000502:physiology*; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D008970:Molecular Weight; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000235:genetics*; D017451:Receptors, Somatomedin; D014452:Ubiquitins / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D014452:Ubiquitins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II