Milk-borne epidermal growth factor modulates intestinal transforming growth factor-alpha levels in neonatal rats

Epidermal growth factor (EGF) is present in milk from various mammalian spe cies, but its physiologic function in neonatal development remains unclear. Transforming growth factor-alpha (TGF-alpha) is a peptide structurally rel ated to EGF, and its presence is detected in the developing small intestine of rats. The purpose of the present study was to examine the effect of mil k-borne EGF on endogenous production of EGF and TGF-alpha in the small inte stine of suckling rats. Neonatal rats were fed via gastrostomy either growt h factor-free rat milk substitute (RMS) or RMS supplemented with EGF (100 n g/mL of RMS) from 8 to 12 d age. Artificially reared rats were then compare d with their dam-fed littermates. Animals fed the EGF-deficient diet RMS ha d markedly increased EGF and TGF-alpha mRNA levels in duodenum and ileum co mpared with dam-fed controls and significantly elevated total intestinal co ntent of TCF-alpha peptide. Intestinal EGF content and EGF serum levels wer e significantly decreased in the RMS group compared with controls. The addi tion of EGF to the RMS diet normalized. TCF-alpha mRNA levels in the duoden um and ileum, EGF mRNA levels in the ileum, and total intestinal TGF-alpha content and EGF serum levels to the levels measured in dam-fed littermates. Motility studies showed that enteral administration of EGF did not affect stomach emptying and intestinal transit. These studies indicate that exogen ous milk-borne EGF modulates endogenous production of TGF-alpha in developi ng small intestine. It is likely that neither TGF-alpha nor EGF are solely responsible for small intestinal overgrowth of artificially reared neonatal rats.