Biologic effects of epidermal growth factor in human fetal jejunum

Abstract

The influence of epidermal growth factor (EGF) on the differentiation and proliferation of human fetal jejunum was studied in organ cultures. Fetal intestine (11-14-wk gestation) was cultured for 5 days at 37 degrees C in serum-free Leibovitz L-15 medium alone or supplemented with 25, 50, and 100 ng EGF/ml culture medium. The addition of hormone did not modify the morphology of the intestinal explants. Biochemical studies revealed that lactase activity was significantly increased with the addition of 50 and 100 ng EGF/ml culture medium. On the other hand, the increase in sucrase, trehalase, and glucoamylase activities that normally occurs during the culture was repressed in the presence of increasing concentrations of EGF. Deoxyribonucleic acid synthesis was significantly decreased after 5 days of culture even in the presence of the lowest EGF concentration used. Concomitantly, the labeling index of the epithelial cells dropped drastically in the presence of EGF. The EGF-induced variation in DNA synthesis was already evident within 24 h of culture, whereas enzymic modifications occurred only between the third and fifth day of culture. The simultaneous addition of EGF and hydrocortisone (50 ng/ml) did not reveal any synergistic action between the two hormones on the hydrolytic activities of the brush border. However, EGF did inhibit hydrocortisone-stimulated DNA synthesis. The present work provides for the first time some basic data on the influence of EGF on brush border hydrolytic activities and on epithelial cell proliferation of human fetal jejunum. These observations strongly suggest that EGF plays an important role in the fetal development of the human gastrointestinal tract.