Dietary Protein Restriction in Artificially Reared Neonatal Rats Causes a Reduction of Insulin-Like Growth Factor-I Gene Expression*

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Abstract
To determine in neonates the effects of protein restriction on growth, serum IGF-I, and IGF-I gene expression, we adapted a technique for rearing neontatl rats (days 6-18 of life) artificially by continuous infusion of milk through a gastrostomy. The artificially reared (AR) animals were given isocaloric diets containing 8%, 13.5%, or 18% lactalbumin protein. The AR rats were compared to rats reared by their mothers (MR) for 18 days. The growth of AR rats was related to the amount of dietary protein, with the pups given 18% protein having the best growth (25.55 g gained during the 12 days of the study) and those given 8% protein having the worst (13.42 g). The 13.5% protein-fed animals were intermediate in weight gain (18.39 g). The weight gains of the 18% and 8% protein-fed pups were significnatly different from that of the MR animals (18.37 g). An identical pattern of tail length growth was noted among the groups. Mean serum IGF-I concentrations followed the same pattern (MR, 1.66 U/ml on day 18 of life; 18% AR, 2.53; 13.5% AR, 1.52; 8% AR, 1.31). Liver IGF-I mRNA was rank-ordered identically with weight gain and serum IGF-I [MR, 23.10 pg/.mu.g poly(A+) RNA; 18% AR, 27.66; 13.5% AR, 21.02%; 8% AR, 18.76]. Unexpectedly, the 7.5-kilobase IGF-I mRNA size class showed a 2- to 3-fold higher abundance in all groups of AR rats comnpared to that in MR controls (P < 0.01), suggesting that this IGF-I size class is regulated independently of the other species. The reductions in serum IGF-I and IGF-I mRNA during protein restriciton of neonatal rats suggest that these responses are mediated by decreased IGF-I gene expression at the level of transcription or RNA stabilization.