Morphologic distribution of transforming growth factor alpha in the gastrointestinal tract--its presence in neuroendocrine cell type of the colon mucosa.

Abstract

Among the growth factor proteins of the epidermal growth factor (EGF)-family especially the transforming growth factor alpha (TGF-alpha) and EGF can be detected in the mucosa of the gastrointestinal tract. In this study, immunohistochemistry on 15 different human tissue probes of gastrointestinal and colonic mucosa was carried out to visualize possible deposits for TGF-alpha in the mucosa and to compare different compartments of the upper and lower gastrointestinal epithelium. Most interestingly, in the colon there is a strong TGF-alpha-like immunoreactivity in neuroendocrine cells as evidenced by double labeling experiments with common neuroendocrine markers and by immunoelectron microscopy. In the upper gastrointestinal epithelium, however, all neuroendocrine cell types are negative for TGF-alpha, but parietal cells of the gastric corpus epithelium show strong cytoplasmic immunostaining for TGF-alpha. The neuroendocrine cells of the colon-harboring TGF-alpha-like immunoreactivity in their neurosecretory granules belong morphologically to the so-called L-cell type. Along with the well-known presence of EGF-receptor in the mucosa of the gastrointestinum, TGF-alpha, which is very likely to be released by this neuroendocrine cell type of the colon, acts in a paracrine mode. These findings represent the first morphologic indication that in the colonic epithelium growth regulation is under neuroendocrine control.