Gastrins are
peptide hormones important for gastric acid secretion and growth of the gastrointestinal mucosa. We have previously demonstrated that ferric
ions bind to
gastrins, that the
gastrin-ferric ion complex interacts with the
iron transport protein transferrin in vitro, and that circulating
gastrin concentrations positively correlate with
transferrin saturation in vivo. Here we report the effect of long-term
dietary iron modification on
gastrin-deficient (Gas(-/-)) and hypergastrinemic
cholecystokinin receptor 2-deficient (Cck2r(-/-)) mice, both of which have reduced basal gastric acid secretion.
Iron homeostasis in both strains appeared normal unless the animals were challenged by
iron deficiency. When fed an
iron-deficient diet, Gas(-/-) mice, but not Cck2r(-/-) mice, developed severe
anemia. In
iron-deficient Gas(-/-) mice, massive
splenomegaly was also apparent with an increased number of splenic megakaryocytes accompanied by
thrombocytosis. The expression of the
mRNA encoding the
iron-regulatory
peptide hepcidin, Hamp, was down-regulated in both Cck2r(-/-) and Gas(-/-) mice on a low-
iron diet, but, interestingly, the reduction was greater in Cck2r(-/-) mice and smaller in Gas(-/-) mice than in the corresponding wild-type strains. These data suggest that
gastrins play an important direct role, unrelated to their ability to stimulate
acid secretion, in hematopoiesis under conditions of
iron deficiency.