Circulating gastrin is increased in hemochromatosis

Abstract

Gastric acid production is important in intestinal iron absorption. The peptide hormone gastrin exists in both amidated and non-amidated forms, which stimulate and potentiate gastric acid secretion, respectively. Since non-amidated gastrins require ferric ions for biological activity in vitro, this study investigated the connection between iron status and gastrin by measurement of circulating gastrin concentrations in mice and humans with hemochromatosis. Gastrin concentrations are increased in the plasma and gastric mucosa of Hfe(-/-) mice, and in the sera of humans with HFE-related hemochromatosis. The discovery of a relationship between iron status and circulating gastrin concentrations opens a new perspective on the mechanisms of iron homeostasis.

Figure 1

Circulating gastrin is increased in hemochromatosis. The concentrations of Gamide (A, C, E) and Ggly (B, D, F) in plasma (A, B) and gastric mucosal extracts (C, D) of mice, and in the sera of patients with hemochromatosis (E, F), were measured by radioimmunoassay [14]. Wild-type C57BL/6J (n = 10) or Hfe^-/- (n = 20) mice were fasted overnight before collection of plasma and tissue samples. The total numbers (n = 41 and 40, respectively) and the mean age of the control and HFE groups, and the numbers of male and female patients, were approximately equal. Data are means ± S.E. Statistical significance relative to the control (^*, p < 0.05; **, p < 0.01; #, p < 0.001) was assessed by one-way ANOVA, followed by Student’s t-test with Bonferroni correction.

Figure 2

The observed changes in gastrin concentrations in mice with disordered iron metabolism are not due to structural changes in the gastric mucosa. The morphology (assessed by staining with hematoxylin/eosin (A, B)), and the numbers of gastric parietal cells (assessed by staining for the gastric H⁺/K⁺-ATPase (C, D)), were the same in wild-type (A, C) and Hfe^-/- (B, D) mice. The scale bar in A represents 50 μm; panels A-D are at the same magnification. Similarly the changes in gastrin concentration were not due to an increased pH, as the pH of the luminal contents (E) was lower in the Hfe^-/- mice than in controls.