Investigation of the role of insulin-like growth factor (IGF)-I and IGF-binding proteins in intestinal and somatic growth regulation in pigs

Insulin-like growth factor (IGF)-I mediates the growth promoting effects of growth hormone and is bound to one of six high affinity IGF binding proteins (IGFBPs) that control its biological action. The importance of IGFBPs and IGF-I in the regulation of somatic and intestinal growth was studied in pigs weaned into a reduced infection pressure (SEW) vs. conventional (CON) rearing environment. SEW pigs grew faster (P < 0.01) than CON pigs. Weaning resulted in a large decrease in the levels of IGF-I and IGFBP-3 and an increase in IGFBP-1 in the circulation for both groups of pigs. Weaning decreased hepatic IGF-I and IGFBP-3 mRNA, increased intestinal IGF-I, but did not change intestinal IGFBP-3 mRNA. Hepatic IGF-I and IGFBP-3 mRNA abundance was uncoupled from levels of IGF-I and IGFBP-3 in plasma. Higher levels of plasma IGF-I and IGFBP-3 were associated with improved growth in SEW pigs. Increased hepatic IGFBP-2 mRNA expression along with elevated plasma IGFBP-2 levels were associated with attenuated growth in CON pigs, suggesting that IGFBP-2 is a negative regulator in somatic growth. Weaning was associated with increased IGF-I mRNA and decreased IGF-I receptor mRNA coincident with a reduction in the number of IGF-I receptors in intestine. The intestinal IGF-I (31%, P < 0.01) and IGFBP-5 (24%) mRNA level were higher in SEW than in CON pigs at 3 d post-weaning. In contrast, SEW pigs showed lower abundance of IGF-I (15%) and IGFBP-5 (40%, P < 0.05) mRNA than CON pigs at 34 d of age, probably reflecting the effect of lower infectious pressure. Scanning electron microscopy and AB/PAS staining revealed a thick mucus coating over the gut epithelium in CON pigs, which was not present in SEW pig, reflecting an increased pathogen load in the gut of CON pigs. Furthermore, SEW pigs showed higher activities of brush border enzymes, ratios of mucosal protein to DNA and villus height to crypt depth compared with CON pigs at 34 d of age. The results demonstrate that: (1) weaning and weaning environment alter expression of intestinal IGF-I and IGFBPs; (2) SEW induces advanced post-weaning gut maturation; (3) the concentrations of plasma IGFBP-2 may play a negative role in somatic growth regulation, whereas IGFBP-3 and IGF-I plasma level may be a positive regulator of somatic growth