PERINATAL EXPRESSION OF TYPE-I IGF RECEPTORS IN PORCINE SMALL-INTESTINE

The gastrointestinal tract of the pig undergoes enhanced growth as well as morphological and functional differentiation during the perinatal period. Concurrently, porcine neonates ingest physiologically significant amounts of insulinlike growth factor-I (IGF-I) via colostrum and milk. The objectives of this study were to examine newborn pig small intestine for the presence of high affinity, IGF-I receptors and to evaluate the possible contributions of maternally derived and locally produced IGF-I to receptor-mediated postnatal growth of intestine. The specific binding of125I-IGF-I to membranes prepared from scraped intestinal mucosa was time, temperature, and pH dependent: Optimal conditions were 48 h, 4 C, and a pH of 7.8, respectively. Several pure peptides were evaluated for competition with125I-IGF-I in binding to intestinal membrane sites. The relative order of competition was IGF-I > insulin-like growth factor-II (IGF-II) > insulin, whereas bombesin and epidermal growth factor were noncompetitive. Chemical cross-linking of126I-IGF-I to binding sites, followed by denaturing SDS-PAGE and autoradiography, demonstrated labeled protein complexes of Mrs 135, 000 and 260, 000. Both autoradiographic bands were diminished when excess unlabeled IGF-I or IGF-II was included in the binding step. Insulin at higher concentrations also slightly inhibited labeling of both membrane proteins. Membranes prepared from intestinal mucosa of piglets at days 0 (less than 2-h old, colostrum-deprived), 3, 5, and 21 postnatal were evaluated for developmental variations in specific binding of125I-IGF-I. Binding was highest at birth, declined (—43%) by day 3, remained low at day 5, and increased by day 21. Receptor affinity was relatively invariant whereas receptor number (per mg membrane protein) was variable. Intestine wt increased disproportionately to body wt between days 0 to 3, postnatal. Radioimmunoassay of extracts of the corresponding intestinal mucosa revealed a significant increase in content of IGF-I by day 3 (P = 0.05), whereas RNA dot-blot hybridization demonstrated low and unchanging IGF-I mRNA abundance in intestine. The quantitative variations in IGF-I protein content and IGF receptor numbers temporally coincide with intestinal villous growth, cessation of intestinal transport of macromolecules (closure), and onset of maturation of intestinal function. © 1990 by The Endocrine Society.