Postnatal catch-up growth induced by growth hormone and insulin-like growth factor-I in rats with intrauterine growth retardation caused by maternal protein malnutrition

Abstract

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 μg/g of body weight (BW)/day), human IGF-I (1.8 μg/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-1 (-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 rots 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 catchup growth in rats with intrauterine growth retardation caused by gestational protein malnutrition.