Gastrin-Deficient Mice Have Disturbed Hematopoiesis in Response to Iron Deficiency
- Author(s)
- Kovac, S; Anderson, GJ; Alexander, WS; Shulkes, A; Baldwin, GS;
- Details
- Publication Year 2011-08,Volume 152,Issue #8,Page 3062-3073
- Journal Title
- ENDOCRINOLOGY
- Publication Type
- Journal Article
- Abstract
- 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 wildtype 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. (Endocrinology 152: 3062-3073, 2011)
- Publisher
- ENDOCRINE SOC
- Keywords
- GLYCINE-EXTENDED GASTRIN; CHOLECYSTOKININ-B/GASTRIN RECEPTORS; FERRIC IONS; HYDROCHLORIC-ACID; HUMAN-ERYTHROPOIETIN; BIOLOGICAL-ACTIVITY; REGULATORY PEPTIDE; FOOD IRON; IN-VIVO; HEPCIDIN
- Publisher's Version
- https://doi.org/10.1210/en.2010-1474
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- Refer to copyright notice on published article.
Creation Date: 2011-08-01 12:00:00