Mechanisms of oral IGF-I induced intestinal growth and lactase specific activity in the neonatal piglet

We have shown that oral IGF-I stimulates ileal villus growth and lactase (LPH) specific activity throughout the small intestine of neonatal piglets. Our goal herein was to investigate the mechanisms of these effects by 1) measuring LPH specific activity, gene expression, and LPH isoform abundance by immunoprecipitation: and 2) assessing mitogenesis using in vivo 5-bromo-2′-deoxyuridine (BrdU) incorporation. Cesarean-derived piglets were fed formula containing 0 or 1000 μR IGF I/L. Piglets were injected intraperitoneal with 50 mg/kg BrdU 48 h prior to termination. After 7 or 14 d, samples were taken along the entire length of the small intestine. Body wt gain and intestinal wt, length, and mucosal mass were unaffected by oral IGF-I. LPH specific activity was 65% higher in piglets fed IGF-I than control (p<0.05). This was accompanied by a 55% higher abundance of the proLPH 260 kDa isoform (p<0.05) and 40% higher LPH mRNA expression in IGF-I treated piglets than control (p< 0.05), suggesting that IGF-I regulates LPH at the level of gene expression, as well as post-transcriptionally, Jejunal and ileal protein and DNA content were measured and BrdU incorporation assessed immunohistochemically. Protein content was unaffected by oral IGF-I, however, ileal DNA content and BrdU labeled nuclei were higher in 14 d IGF-I-treated piglets than control (p<0.05), supporting our previously observed increased villus height in response to oral IGF-I. In conclusion, orally administered IGF-I modulates LPH transcription and translation and villus growth by stimulating crypt mitogenesis. (Supported by HD 29264).