Developmental expression of transforming growth factor-alpha and epidermal growth factor receptor proteins in the human pancreas and digestive tract.

This study was designed to localize transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) expression in the developing human gastrointestinal tract and pancreas. Immunohistochemical techniques using specific antibodies against human TGF-alpha and EGFR were performed on digestive tissues of fetuses from 9 to 10 to 24 weeks of gestation, children and adults. In fetuses, TGF-alpha and EGFR proteins were expressed in all epithelial tissues studied with a good correlation and from an age as early as 9 to 10 weeks of gestation, except for TGF-alpha in the esophagus. The strongest TGF-alpha immunostaining was noted in the stomach and the proximal colon. Unexpectedly, immunoreactive gut endocrine cells were observed with the two antibodies used. Relatively numerous in fetuses, they decreased in number with age and were rare in adults particularly along the colon. Enteroglucagonsecreting cells were shown to express TGF-alpha, while some gastrin, somatostatin and pancreatic glucagon cells were immunostained with EGFR antibodies. The presence of TGF-alpha and its receptor in digestive tract epithelium and pancreatic tissues early in fetal life suggests a functional role for TGF-alpha during the developmental process of the digestive system. We demonstrate that TGF-alpha is also produced by endocrine cells and might have an additional mode of action other than paracrine, at least during fetal life.