Ghrelin Expression in Hyperplastic and Neoplastic Proliferations of the Enterochromaffin-like (ECL) Cells

Abstract

Ghrelin, a recently discovered peptide isolated from the gastric corpus mucosa, is believed to be important in the regulation of growth hormone secretion and has been shown to increase appetite and food intake as well. It may also have other gastrointestinal and cardiac functions. Because a cell of origin for ghrelin has not been convincingly identified in the gastric mucosa thus far, we studied the immunohistochemical expression of ghrelin in proliferative lesions of the enterochromaffin-like (ECL) cells-a cell that is not only exclusively confined to the gastric corpus mucosa but is its dominant endocrine cell type as well. Formalin-fixed, paraffin embedded tissues from three cases of gastric ECL cell hyperplasia and five ECL carcinoids (three with coexisting foci of diffuse, linear, and micronodular hyperplasia) were immunohistochemically stained for ghrelin, using a commercially available antibody. The Sevier-Munger stain for ECL cells and immunohistochemical stains for chromogranin, gastrin, serotonin, somatostatin, and vesicular monoamine transporter-2 (VMAT-2) were performed on parallel sections for correlation with the ghrelin staining results. All ECL cell carcinoids and hyperplastic lesions were positive for both the Sevier-Munger and the immunohistochemical stains for chromogranin and VMAT-2. Immunoreactivity for ghrelin was seen in 4/5 ECL carcinoids, all cases of ECL cell hyperplasia, as well as in all areas with linear and micronodular hyperplasia adjacent to the ECL cell carcinoids. In each instance, such staining was confined to the Sevier-Munger, and VMAT-2 positive cells only. Our findings indicate that the ECL cells are either the ghrelin-producing cells of the gastric mucosa or acquire the capability to synthesize ghrelin during proliferative states encompassing the entire hyperplasia to neoplasia spectrum. In view of the orexigenic and other known actions of ghrelin, the functional and/or biologic significance of ghrelin production in such ECL cell proliferations needs to be investigated further.

PACAP intraperitoneal treatment suppresses appetite and food intake via PAC1 receptor in mice by inhibiting ghrelin and increasing GLP-1 and leptin

“…Dopamine, which is substantially produced in the GI tract, was demonstrated to stimulate ghrelin secretion via its D1A receptors (20). Although PACAP and PAC1 expression has not yet been identified on PD/1 cells of the gastric fundus, PAC1 receptors have been characterized on ECL cells (61), which have been shown to secrete ghrelin (48). Further knowledge on ghrelin secretion processes is currently limited due to the difficulty of pure gastric mucosa cells isolation techniques (22).…”

Ghrelin Gene Products and the Regulation of Food Intake and Gut Motility

“…The expression of obestatin was positively correlated with that of ghrelin in normal and tumorous samples. An immunohistochemical study demonstrated ghrelin immunoreactivity in enterochromaffin-like cells of human stomach, and the authors speculated that gastric enterochromaffin-like cells acquired the capacity to secrete ghrelin early in their hyperplasia-neoplasia sequence (Srivastava et al, 2004). Collectively, these emerging data suggest that ghrelin gene products and their related coupled receptors may play roles (either promoting or inhibiting) in promoting tumor growth via an autocrine/paracrine pathway.…”

Plasma ghrelin concentrations in type 1 diabetic patients with autoimmune atrophic gastritis

“…Pernicious anaemia (PA) is considered to be the end stage of type A CAG. Immunohistochemical studies have revealed ghrelin expression in gastric neuroendocrine (NE) cell hyperplasia lesions of type A CAG patients (8,9) and gastric carcinoid tumours (10), although scarce data exist about plasma ghrelin concentrations in these patients. We recently reported that DM1 patients present an increased prevalence of latent pernicious anaemia when low plasma pepsinogen I concentrations are considered the main marker of early gastric mucosa atrophy (11).…”