Role of insulin-like growth factors and type I receptors in the developing porcine intestine
The role of the IGF system during intestinal development of the pig, and in particular the significance of dietary IGF-I was investigated. Significant concentrations of IGF-I and IGFBP were measured in milk and colostrum and in vitro immunoaffinity chromatography studies confirmed IGF-I stability in the presence of newborn and suckled intestinal contents. Specific IGF-I receptors were identified on apical and basolateral membranes, and the cytoplasm of villus/crypt enterocytes. Receptor binding data revealed binding to a single site, with an affinity of 1nM. Receptor affinity remained constant during development but in apical microvillar membranes, IGF-I receptors were transiently up-regulated in suckled animals. The specificity of receptors was confirmed using competition binding and affinity crosslinking studies, and the functional activity of receptors demonstrated using an in vitro receptor autophosphorylation assay. In Caco-2 intestinal cells IGF-I binding and IGF-I receptor mRNA expression was significantly increased in the presence of 7 and 14 day milk, suggesting that milk-borne factors may regulate the up-regulation observed in vivo. In vivo experiments were undertaken using colostrum-fed and colostrum-deprived artificially-reared pigs. Significant differences in plasma IGF-I and IGF binding proteins were observed in the IGF- treated animals compared to controls suggesting that IGF-I remained bioactive in the intestine and was transported to the circulation. The in vivo effects of IGF-I were modulated by early nutrition. Plasma IGF-I increased in colostrum-deprived animals, whereas in colostrum-fed animals levels decreased.