Minimal hydrolysis of epidermal growth factor by gastric fluid of preterm infants

Epidermal growth factor (EGF), present in high concentrations in milk, may play a role in growth of the gastrointestinal tract. Resistance to proteolytic degradation in the stomach is necessary if ingested EGF is to function within the gastrointestinal tract. Although EGF stability to low pH and proteases predicts gastric survival, the extent of digestion in the stomach remains to be defined. Consequently, we measured gastric degradation of 125I-human recombinant EGF in preterm infants with an in vitro method in which EGF was incubated at 37 degrees C with stomach fluid at pH 1.8, 3.2, and 5.8 followed by analysis of degradation products. As maximal acid proteolytic activity is present one hour after feeding in preterm infants, fluid was obtained at that time from 18 infants with a mean gestational age at birth of 30.4 (3.0) (SD) weeks and a postnatal age of 26.3 (12.7) days at sampling. Incubations for up to 60 minutes revealed minimal loss of trichloroacetic acid precipitable radioactivity, in contrast to the substantial hydrolysis of iodinated casein which occurred under the same conditions. Chromatography of reaction mixtures on Sephadex G-25 showed a single major peak of radioactivity which coeluted with EGF. Epidermal growth factor also retained greater than 75% of its ability to bind to anti-EGF affinity columns and placental membrane receptors after incubation with gastric fluid. These data support the concept of substantial gastric survival of ingested EGF in a potentially biologically active form in preterm infants.