Epidermal growth factor does not act as a primary cue for inducing developmental changes in suckling mouse jejunum.

Abstract

The direct influence of epidermal growth factor (EGF) on the differentiation and proliferation of small intestine was studied in organ culture. Eight-day-old mouse small intestine was cultured during 2 days in serum-free Leibovitz L-15 medium alone or supplemented with EGF (50, 100, and 500 ng/ml) either at room temperature or at 37 degrees C. Brush border membrane hydrolytic activities, namely, sucrase, lactase, glucoamylase, trehalase, maltase, and alkaline phosphatase, were assayed in the intestinal tissue as well as in the culture medium. None of the brush border enzymic activities was affected by the addition of EGF to the culture medium. This lack of effect is not temperature dependent since it occurred both at room temperature and at 37 degrees C. The addition of hydrocortisone (10(-6) M) to the culture medium induced the appearance of sucrase activity and increased the activity of the other brush border enzymes. The simultaneous addition of EGF with hydrocortisone did not influence the response of the intestinal explants to hydrocortisone. The deoxyribonucleic acid (DNA) content was determined while DNA synthesis was evaluated by the incorporation of (3H)-thymidine. The addition of EGF did not affect DNA content or (3H)-thymidine incorporation into DNA either at room temperature or at 37 degrees C. The EGF binding to epithelial cells did not significantly vary throughout the culture period and a down-regulation process occurred in presence of EGF. These observations strongly suggest that EGF does not act as a primary cue for inducing developmental changes in suckling mouse small intestine. It is proposed that EGF induces a systemic reaction in vivo that then influences the neonatal small intestine.