Abstract 1696 Human Milk Poster Symposium, Sunday, 5/2

Insulin-Like Growth Factor-I (IGF-I) is a potent mitogenic peptide believed to be involved in postnatal growth regulation. In addition to endogenous production, sucklings of many species, including the rat, ingest significant quantities of IGF-I in breast milk. In recent work from our laboratory, we have demonstrated that sucklings fed an artificial diet + IGF-I had serum IGF-I levels similar to dam fed controls and 2X that of animals fed the artificial diet alone. We examined the Hypothesis that IGF's may be absorbed in bioactive form from the gastrointestinal tract (GIT) to the portal circulation and beyond. The experimental design consisted of using fasted suckling rats (10 days, n=22). Radiolabelled recombinant human IGF-I (rh 125I-IGF-I 4×106 cpm, 100 µl volume) was given in a 1:1 mixture of appropriate aged rat milk via orogastric tube at time "0." At 5, 10, 20, and 30 minutes post administration, portal blood was obtained by venipuncture while under anesthesia. Within 30-60 seconds after portal venipuncture, paired peripheral blood samples were also removed. Blood specimens were weighed to determine volume and counted in a gamma counter to determine radioactivity (cpm). Radioactivity was standardized to cpm/100µl of blood to account for differences in volume of blood obtained at venipuncture. Results show that IGF-I radioactivity in portal blood was higher than in peripheral blood and was maximal at 20-30 min post ingestion. Size exclusion gel chromatography was performed on all samples and confirmed that in portal blood from times 5-30 min, 20-25% of cpm eluted in the position of "native" IGF-I. However, a significant peak corresponding to IGF in peripheral blood samples could only be found at 5 min post ingestion. Portal blood peaks using HPLC were identical to the gel elution position of rhIGF-I. In addition, selected peak fractions from portal blood isolates were exposed to a competitive binding assay using a placental membrane preparation bearing IGF-I receptors. This assay confirmed the presence of receptor active IGF-I in portal blood from animals fed the radiolabelled IGF-I preparation. We conclude that milk-borne IGF-I is absorbed from the GIT of the suckling rat into portal blood. Furthermore, since we have previously demonstrated that intravenously injected IGF-I passes into bile in a receptor active form in the infant rat (Kong, et al, Biol Neonate 71:239-250, 1997), this latter series of studies lends credence to the concept of an enterohepatic circulation for IGF in the suckling. Supported by NIH grant P01-HD-26013