Role of insulin-like growth factors in intrauterine and postnatal growth retardation caused by gestational protein malnutrition in the rat
(1995)
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- In order to evaluate the hypothesis that nutrition-induced intrauterine and postnatal growth retardation could be due to alterations in insulin-like growth factors (IGFs) and their binding proteins (IGFBPs), we examined in a rat model the specific effects of maternal dietary protein restriction (25% of the protein intake of the control pregnant rats) on the growth indices of the progeny in relation to the effects on IGFs and IGFBPs. <BR> The adverse effects of gestational protein malnutrition on fetal growth parallel changes in circulating fetal IGF-I; plasma IGF-I being normal in fetuses or neonates whose growth is not affected by maternal protein deficiency, and significantly reduced in the growth-retarded newborn pups. Furthemore, the reduction in plasma IGF-I of these pups reflects the degree of intrauterine growth retardation (IUGR), and is accompanied by parallel decreases in liver IGF-I peptide and mRNA. Taken together, our findings support the hypothesis that reductions on IGF-I production and/or availability contribute to stunting of fetal growth, and that decline in neonatal plasma IGF-I may be mediated through decreased expression of the IGF-I gene. In constrast, plasma IGF-II and liver IGF-II gene expression, plasma IGFBPs, insulin and GH cncentrations are not affected in the growth-retarded newborn pups after gestational protein malnutrition. Our studies, therefore, do not support a major role for IGF-II in the nutritional regulation of fetal growth, especially in nutrition-induced IUGR. <BR> The long-term adverse of gestational protein malnutrition on postnatal growth of the progeny are also accompanied by parallel changes in circulating and liver concentrations of IGF-I, suggesting that this growth factor plays a pivotal role in the catch-up growth process after prenatal nutritional insult. There is, however, no concomitant alteration in liver IGF-I mRNA concentrations, serum IGFBPs, insulin and GH concentrations, suggesting that reduced IGF-I in these animals results more from a translational defect on IGF-I synthesis than from a persistent alteration of gene expression. Direct evidence for a role of IGF-I in postnatal growth retardation following IUGR is provided by our studies showing that restoration of normal serum IGF-I concentrations by exogenous IGF-I treatment in neonatal rats with IUGR and nutritional rehabilitation, induces postnatal catch-up growth. Similar effects are also observed under GH therapy which increases endogenous IGF-I production
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Muaku, M. M. (1995). Role of insulin-like growth factors in intrauterine and postnatal growth retardation caused by gestational protein malnutrition in the rat. https://hdl.handle.net/2078.5/111175