HYPERGASTRINEMIA AND GASTRIC ENTEROCHROMAFFIN-LIKE CELLS

The enterochromaffin-like (ECL) cell of the oxyntic, acid-secreting mu cosa is at present the most extensively studied endocrine cell type in the gastrointestinal tract. It is functionally related to acid secret ion through paracrine release of histamine. Its ability to undergo pro liferation in response to the trophic stimulus of hypergastrinemia has important implications in pathology, being involved in the developmen t of ECL-cell carcinoid tumors of rodents treated with powerful inhibi tors of acid secretion as well as in that of most human gastric carcin oids which, with rare exceptions, are composed of ECL cells. The vario us aspects of the ECL-cell response to hypergastrinemia in humans are discussed in this review. The trophic effect of gastrin is specific fo r ECL cells and its sensitivity is enhanced by the female sex and by t he genetic background of the multiple endocrine neoplasia type 1 (MEN- 1) syndrome. Exposure of ECL cells to hypergastrinemia induces peculia r changes in the structure of cytoplasmic granules and triggers the ph enotypic expression of a novel protein, the a subunit of glycoprotein hormones, absent in normal cells. The ECL-cell hyperplasia driven by h ypergastrinemia may influence the hypersecretory gastric state of pati ents with Zollinger-Ellison syndrome (ZES) by inappropriate intramucos al secretion of histamine and may contribute to the high circulating l evels of basic fibroblast growth factor (bFGF), an ECL-cell product re sponsible for parathyroid mitogenic effects in MEN-1 patients. However , hypergastrinemia per se cannot promote evolution of hyperplasia into carcinoid tumors, for which additional unknown factors, particularly associated with atrophic gastritis or MEN-1 syndrome, are required. EC L-cell carcinoids developing within these backgrounds have a strikingl y more favorable course than their gastrin-independent counterpart. Su ppression of hypergastrinemia, either by antrectomy or treatment with somatostatin analogues, may induce regression of both ECL-cell hyperpl asia and gastrin-sensitive ECL-cell carcinoids.