Abstract 672 Poster Session III, Monday, 5/3 (poster 174)

A diverse number of growth factors and other biologically active substances are present in mammalian milk. Among these are the peptides IGF-I and -II. These factors, which share homology with proinsulin and each other, are thought to be important in growth regulation, including during the perinatal period. However, it remains unclear whether or not milk-borne IGF's play a biological role in development of the suckling. In order to study the effects of these peptides, we fed suckling rats (from d 8-12) by gastrostomy a growth factor free Rat Milk Substitute (RMS) with or without physiological amounts of rhIGF-I or -II. Results: Body weights and skeletal growth (tail length) were similar between the groups at the end of the study period. Liver weight was significantly (p<0.01) increased over RMS fed rats in the IGF-II but not the IGF-I fed group. However, both IGF-I and -II were associated with relative increases in proximal and midjejunal weights and protein contents in comparison to the RMS group or to mother fed controls (p<0.05). Proximal and midjejunal sucrase activities were increased in IGF-I supplemented rats above RMS fed controls. Smaller but insignificant changes were noted in intestinal sucrase activity in IGF-II fed animals. No differences in sucrase activities among the experimental groups were observed in distal small intestine. A series of histological studies were performed on tissues from these animals as well. Intestinal epithelial cell crypt depth was increased in both groups of IGF-supplemented animals. Small intestinal villus height was moderately increased but was only significantly elevated above controls in IGF-II fed sucklings. Serum glucose concentrations were highest in dam fed rats and lowest in the RMS group (189±21 vs 105±13 mg/dl, p<0.05) and were intermediate in both IGF fed groups (153±10 and 150±4 mg/dl). We conclude that milk borne IGF-I and -II, when given in physiological concentrations, induced stimulation of intestinal growth in suckling rats and that IGF-II has a specific effect on hepatic growth. Results of IGF supplementation on intestinal growth and sucrase activity in the suckling suggest a luminal concentration-dependent effect (ie proximal > distal). The AR suckling rat may be useful as a model in studying the potential benefit of supplementing artificial human formulas with IGF for very premature babies.

Supported by NICHD P-01 #HD26013