No abstract

/We examined the effects of maternal dietary protein restriction on fetal growth and expression of IGF-I and -11, and ' IGF-binding proteins (IGFBP). We sought to dissociate the , respective effects of maternal protein versus calorie restriction on growth indices and IGF synthesis by the neonates of proteinrestricted dams. Pregnant Wistar rats (six to eight per group) fed a low (5%) protein diet throughout gestation had impaired body weight gain compared with controls fed a normal (20%) protein diet (by 45%, p < 0.001). Their serum and liver IGF-I concentrations and liver IGF-I mRNA concentrations were also reduced by 60, 80, and 50%, respectively. Serum IGFBP-3 was reduced by 60% in protein-restricted dams within 1 to 2 h after delivery ( p < 0.001 versus controls), although IGFBP-1, -2, and -4 were not significantly affected by the dietary protein intake. In pups of ' protein-restricted dams, the mean body and liver weight at birth was 15-20% less than that observed in the progeny from normal protein-fed dams ( p < 0.01). Their plasma and liver IGF-I concentrations were 30 and 60% lower, respectively, whereas, liver IGF-I mRNA abundance was reduced by 50% ( p < 0.01).In contrast, neonatal plasma IGF-I1 and liver IGF-I1 mRNA concentrations wen: not significantly affected by the maternal protein malnutrition. Also, the plasma levels of IGFBP were not altered in the growlh-retarded pups. There is also evidence that the IGF may regulate fetal growth and differentiation. IGF and their mRNA are present in most fetal tissues (2-4); specific IGF receptors and IGFBP are widely expressed during fetal life (5); and IGF exert mitogenic

In this study, we examined the effects of exogenous IGF-I and GH on postnatal growth of rat pups with intrauterine growth retardation due to gestational protein restriction. From birth until weaning (d 23), pups born from dams fed ad libitum a low (5% casein; P5 pups) or a normal protein diet (20% casein; P20 controls) were cross-fostered to well nourished lactating dams. On d 2, the litters (n = 6/dietary group) were reduced in size to 6 pups, and littermates received, through postnatal d 23, two daily s.c. injections of bovine GH (2.5 microg/g of body weight (BW)/day), human IGF-I (1.8 microg/g of BW/day), or saline. At birth, BW and tail length (TL) of P5 pups were markedly decreased (to 72 and 70% of controls, respectively; p < 0.001). Despite food rehabilitation, stunting of body growth was still apparent on d 23 in the saline-injected P5 rats (BW and TL: 76 and 83% of age-matched saline-injected controls; p < 0.01). Serum IGF-I (-51%; p < 0.001) and weight of liver, heart, kidney, brain, and thymus (-13 to -35%; p < 0.01) were also reduced. Administration of GH in P5 rats raised their serum IGF-I (1-fold) to levels observed in saline-injected controls, and restored normal BW and TL (94 and 98% of controls, respectively), and organ weight (91-107% of those of controls). Injections of IGF-I in P5 rats increased after 1 h their serum IGF-I to levels 3 times greater than in saline-injected controls, and resulted in normalization of BW and TL (94 and 96% of controls), and organ weight (92-111% of controls). In P20 controls, 3-wk GH and IGF-I injections significantly increased serum IGF-I (0.6- and 2-fold increases, respectively), BW (14 and 11%), TL (12 and 11%), and organ weight (+10 to 30%) compared with saline-injected rats (p < 0.01). We conclude that under conditions of adequate nutrition, both GH and IGF-I may equally promote postnatal catch-up growth in rats with intrauterine growth retardation caused by gestational protein malnutrition.

We examined the long-term effects of dietary protein restriction during rat pregnancy on serum IGF-I, serum IGF binding proteins, and liver IGF-I gene expression during postnatal development. Pregnant Wistar rats were fed ad libitum throughout gestation a normal (20% casein diet; P20 controls) or a low (5% casein; P5) protein diet. At birth, the pups from both P20 and P5 dams were cross-fostered to well nourished lactating dams, and litters (n = 5/dietary group) were reduced in size to 6 pups. After weaning (d 22), the pups were fed the control diet ad libitum. The pups were killed at 8, 22, and 63 d of age. Gestational protein restriction caused significant growth retardation and mortality in newborn pups. Despite food rehabilitation during the suckling period (d 0-22), body weight, tail length, and the weight of liver, heart, kidney, and brain in the P5 pups remained significantly reduced at 8 and 22 d (-17 to -35%) compared with control pups. At the same time, serum and liver IGF-I concentrations in the P5 pups (on d 8: 100 +/- 9 ng/mL and 11 +/- 1 ng/g, respectively; on d 22: 340 +/- 20 ng/mL and 42 +/- 3 ng/g) were lower than in age-matched controls (on d 8: 170 +/- 12 ng/mL and 26 +/- 2 ng/g; on d 22: 470 +/- 30 ng/mL and 73 +/- 5 ng/g), although liver IGF-I mRNA abundance was not affected. After long-term food rehabilitation (d 63), tail length and organ weight recovered, and serum and liver IGF-I concentrations were normalized. However, although the P5 rats had resumed a normal growth rate, their body weight remained lower than in the controls. There were no differences in serum IGF binding proteins 1-4, insulin, and GH concentrations between the groups at any age studied. These results suggest that reduction in serum IGF-I may contribute to the reduced somatic and organ growth observed in rats after gestational protein malnutrition, and further support a role for IGF-I in the control of catch-up growth.