Insulin-like growth factors and the developing and mature rat small intestine: receptors and biological actions.

To determine if insulin-like growth factor-I (IGF-I) or multiplication stimulating activity (MSA, rat IGF-II) might directly influence small intestinal epithelium, we studied the distribution of IGF binding sites during development of the rat intestine. Cell membranes from suckling rat mucosa bound 2–6 times as much 125I-IGF-I and 3–5 times as much 125I-MSA as did adult membranes. Isolated villus cells from suckling and adult rats specifically bound both IGFs. IGF-I binding tended to remain high during suckling, whereas MSA binding fell progressively from the early suckling period. Competitive displacement studies with insulin, IGF-I and MSA demonstrated the presence of type-I and type-II IGF receptors. In vitro autoradiography of 125I-IGF-I binding sites in adult and suckling rat jejunum showed highest binding in the submucosa with extensions up into the lamina propria. Immunocytochemical localization of type-II receptors showed highest density in villus epithelium and vessel walls. Administration of MSA by oral and IGF-I by oral and parenteral routes (1 µg/day for 6 days) to suckling rats stimulated jejunal brush border enzymes, but not intestinal growth. Developmental changes in receptor density and effects on brush border enzymes suggest a specific role for IGFs in post-natal development of the rat intestine.