Epidermal growth factor and postnatal development of intestinal transport and membrane structure

The effects of epidermal growth factor (EGF) on postnatal development of intestinal transport and the physical composition of the microvillus membrane were examined. New Zealand White rabbits received EGF (40 micrograms/kg/d) from d 3 of life to d 17 either intraperitoneally or orogastrically. Intestinal H2O, Na+, and glucose absorption expressed per cm of intestine were significantly increased in animals receiving EGF by either route. When EGF was given by the orogastric route, nutrient absorption rates normalized to mucosal DNA were not elevated; thus, increased absorption induced by orogastric EGF appeared to be secondary to mucosal hyperplasia. In contrast, systemic EGF up-regulated cellular nutrient transport. To evaluate at which membrane level these changes occurred, brush border membrane vesicles were isolated from both the jejunum and ileum of control and EGF-treated animals. Rates of Na(+)-dependent glucose transport into the vesicles revealed that in the ileum systemic EGF up-regulated maximal rates of glucose transport by 54% without affecting the Km. These observations were associated with alterations in the lipid composition and physical properties of the microvillus membrane. EGF-treated animals had significant reductions in membrane cholesterol content and altered ratios of phospholipid subclasses. The net result of these variations was that the microvillus membrane isolated from EGF-treated animals was significantly more fluid than membrane from controls. Thus, these results suggest that EGF modulates development of transport function during the postnatal period both by stimulating mucosal growth and by inducing specific transport processes. Furthermore, these changes are associated with alterations in the physical composition of the microvillus membrane.