{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T10:40:46Z","timestamp":1790160046349,"version":"4.1.0"},"reference-count":51,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,8,1]]},"abstract":"<jats:p>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\u2212\/\u2212) and hypergastrinemic cholecystokinin receptor 2-deficient (Cck2r\u2212\/\u2212) 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\u2212\/\u2212 mice, but not Cck2r\u2212\/\u2212mice, developed severe anemia. In iron-deficient Gas\u2212\/\u2212mice, 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\u2212\/\u2212 and Gas\u2212\/\u2212mice on a low-iron diet, but, interestingly, the reduction was greater in Cck2r\u2212\/\u2212 mice and smaller in Gas\u2212\/\u2212 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.<\/jats:p>","DOI":"10.1210\/en.2010-1474","type":"journal-article","created":{"date-parts":[[2011,6,8]],"date-time":"2011-06-08T03:22:35Z","timestamp":1307503355000},"page":"3062-3073","source":"Crossref","is-referenced-by-count":12,"title":["Gastrin-Deficient Mice Have Disturbed Hematopoiesis in Response to Iron Deficiency"],"prefix":"10.1210","volume":"152","author":[{"given":"Suzana","family":"Kovac","sequence":"first","affiliation":[{"name":"The University of Melbourne Department of Surgery (S.K., A.S., G.S.B.), Austin Health, Heidelberg, Victoria 3084, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J.","family":"Anderson","sequence":"first","affiliation":[{"name":"Queensland Institute of Medical Research (G.J.A.), Brisbane, Queensland 4029, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren S.","family":"Alexander","sequence":"first","affiliation":[{"name":"Cancer and Haematology Division (W.S.A.), Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Shulkes","sequence":"first","affiliation":[{"name":"The University of Melbourne Department of Surgery (S.K., A.S., G.S.B.), Austin Health, Heidelberg, Victoria 3084, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham S.","family":"Baldwin","sequence":"first","affiliation":[{"name":"The University of Melbourne Department of Surgery (S.K., A.S., G.S.B.), Austin Health, Heidelberg, Victoria 3084, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2011,6,7]]},"reference":[{"key":"2020071612471164600_B1","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/35042073","article-title":"Iron homeostasis: insights from genetics and animal models.","volume":"1","author":"Andrews","year":"2000","journal-title":"Nat Rev Genet"},{"key":"2020071612471164600_B2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev.physiol.69.031905.164337","article-title":"Iron homeostasis.","volume":"69","author":"Andrews","year":"2007","journal-title":"Annu Rev Physiol"},{"key":"2020071612471164600_B3","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1182\/blood.V99.10.3505","article-title":"Regulation of ferritin genes and protein.","volume":"99","author":"Torti","year":"2002","journal-title":"Blood"},{"key":"2020071612471164600_B4","doi-asserted-by":"crossref","first-page":"8780","DOI":"10.1073\/pnas.151179498","article-title":"Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice.","volume":"98","author":"Nicolas","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612471164600_B5","doi-asserted-by":"crossref","first-page":"7811","DOI":"10.1074\/jbc.M008923200","article-title":"A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload.","volume":"276","author":"Pigeon","year":"2001","journal-title":"J Biol Chem"},{"key":"2020071612471164600_B6","doi-asserted-by":"crossref","first-page":"7806","DOI":"10.1074\/jbc.M008922200","article-title":"Hepcidin, a urinary antimicrobial peptide synthesized in the liver.","volume":"276","author":"Park","year":"2001","journal-title":"J Biol Chem"},{"key":"2020071612471164600_B7","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1126\/science.1104742","article-title":"Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization.","volume":"306","author":"Nemeth","year":"2004","journal-title":"Science"},{"key":"2020071612471164600_B8","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1172\/JCI0215686","article-title":"The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation.","volume":"110","author":"Nicolas","year":"2002","journal-title":"J Clin Invest"},{"key":"2020071612471164600_B9","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1006\/bcmd.2002.0573","article-title":"Hepcidin, a new iron regulatory peptide.","volume":"29","author":"Nicolas","year":"2002","journal-title":"Blood Cells Mol Dis"},{"key":"2020071612471164600_B10","doi-asserted-by":"crossref","first-page":"667","DOI":"10.33549\/physiolres.930841","article-title":"Hepcidin mRNA levels in mouse liver respond to inhibition of erythropoiesis.","volume":"55","author":"Vokurka","year":"2006","journal-title":"Physiol Res"},{"key":"2020071612471164600_B11","doi-asserted-by":"crossref","first-page":"3730","DOI":"10.1182\/blood-2006-06-028787","article-title":"Suppression of hepcidin during anemia requires erythropoietic activity.","volume":"108","author":"Pak","year":"2006","journal-title":"Blood"},{"key":"2020071612471164600_B12","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/S0016-5085(81)80013-3","article-title":"Role of gastric acid in food iron absorption.","volume":"81","author":"Skikne","year":"1981","journal-title":"Gastroenterology"},{"key":"2020071612471164600_B13","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/j.1365-2036.1992.tb00553.x","article-title":"Review article: metabolic consequences of long-term inhibition of acid secretion by omeprazole.","volume":"6","author":"Koop","year":"1992","journal-title":"Aliment Pharmacol Ther"},{"key":"2020071612471164600_B14","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1097\/00004836-199206000-00005","article-title":"Serum iron, ferritin, and vitamin B12 during prolonged omeprazole therapy.","volume":"14","author":"Koop","year":"1992","journal-title":"J Clin Gastroenterol"},{"key":"2020071612471164600_B15","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1056\/NEJM196809262791302","article-title":"Effect of hydrochloric acid on iron absorption.","volume":"279","author":"Schade","year":"1968","journal-title":"N Engl J Med"},{"key":"2020071612471164600_B16","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0016-5085(19)34096-X","article-title":"Ascorbic acid chelates in iron absorption: a role for hydrochloric acid and bile.","volume":"55","author":"Conrad","year":"1968","journal-title":"Gastroenterology"},{"key":"2020071612471164600_B17","first-page":"108","article-title":"The importance of gastric hydrochloric acid in the absorption of nonheme food iron.","volume":"92","author":"Bezwoda","year":"1978","journal-title":"J Lab Clin Med"},{"key":"2020071612471164600_B18","first-page":"418","article-title":"Small intestinal regulation of iron absorption in the rat.","volume":"110","author":"Conrad","year":"1987","journal-title":"J Lab Clin Med"},{"key":"2020071612471164600_B19","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1046\/j.1365-2036.1998.00274.x","article-title":"Iron absorption in patients with Zollinger-Ellison syndrome treated with long-term gastric acid antisecretory therapy.","volume":"12","author":"Stewart","year":"1998","journal-title":"Aliment Pharmacol Ther"},{"key":"2020071612471164600_B20","doi-asserted-by":"crossref","DOI":"10.1016\/B978-012088394-3\/50052-0","article-title":"Regulation of gastric acid secretion","author":"Shulkes","year":"2006"},{"key":"2020071612471164600_B21","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/ijc.1483","article-title":"Short term infusion of glycine-extended gastrin(17) stimulates both proliferation and formation of aberrant crypt foci in rat colonic mucosa.","volume":"94","author":"Aly","year":"2001","journal-title":"Int J Cancer"},{"key":"2020071612471164600_B22","first-page":"1","article-title":"Gastrins, cholecystokinins and gastrointestinal cancer.","volume":"1704","author":"Aly","year":"2004","journal-title":"Biochim Biophys Acta"},{"key":"2020071612471164600_B23","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1053\/gast.2000.16480","article-title":"Glycine-extended gastrin synergizes with gastrin 17 to stimulate acid secretion in gastrin-deficient mice.","volume":"119","author":"Chen","year":"2000","journal-title":"Gastroenterology"},{"key":"2020071612471164600_B24","doi-asserted-by":"crossref","first-page":"10741","DOI":"10.1021\/bi010016h","article-title":"Selective, high-affinity binding of ferric ions by glycine-extended gastrin(17).","volume":"40","author":"Baldwin","year":"2001","journal-title":"Biochemistry"},{"key":"2020071612471164600_B25","doi-asserted-by":"crossref","first-page":"48602","DOI":"10.1074\/jbc.M208440200","article-title":"Ferric ions are essential for the biological activity of the hormone glycine-extended gastrin.","volume":"277","author":"Pannequin","year":"2002","journal-title":"J Biol Chem"},{"key":"2020071612471164600_B26","doi-asserted-by":"crossref","first-page":"G220","DOI":"10.1152\/ajpgi.00046.2010","article-title":"Stimulation of proliferation in the colorectal mucosa by gastrin precursors is blocked by desferrioxamine.","volume":"299","author":"Ferrand","year":"2010","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2020071612471164600_B27","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1677\/joe.0.1810315","article-title":"Divergent roles for ferric ions in the biological activity of amidated and non-amidated gastrins.","volume":"181","author":"Pannequin","year":"2004","journal-title":"J Endocrinol"},{"key":"2020071612471164600_B28","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/0003-9861(88)90653-4","article-title":"Interaction of gastrin with transferrin: effects of ferric ions.","volume":"263","author":"Longano","year":"1988","journal-title":"Arch Biochem Biophys"},{"key":"2020071612471164600_B29","doi-asserted-by":"crossref","first-page":"4866","DOI":"10.1111\/j.1742-4658.2009.07186.x","article-title":"Definition of the residues required for the interaction between glycine-extended gastrin and transferrin in vitro.","volume":"276","author":"Kovac","year":"2009","journal-title":"FEBS J"},{"key":"2020071612471164600_B30","doi-asserted-by":"crossref","first-page":"G855","DOI":"10.1152\/ajpgi.90359.2008","article-title":"Interrelationships between circulating gastrin and iron status in mice and humans.","volume":"295","author":"Kovac","year":"2008","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2020071612471164600_B31","doi-asserted-by":"crossref","first-page":"G561","DOI":"10.1152\/ajpgi.1998.274.3.G561","article-title":"Impaired gastric acid secretion in gastrin-deficient mice.","volume":"274","author":"Friis-Hansen","year":"1998","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2020071612471164600_B32","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/S0016-5085(97)90000-7","article-title":"Abnormal gastric histology and decreased acid production in cholecystokinin-B\/gastrin receptor-deficient mice.","volume":"112","author":"Langhans","year":"1997","journal-title":"Gastroenterology"},{"key":"2020071612471164600_B33","doi-asserted-by":"crossref","first-page":"11825","DOI":"10.1073\/pnas.93.21.11825","article-title":"G protein-coupled cholecystokinin-B\/gastrin receptors are responsible for physiological cell growth of the stomach mucosa in vivo.","volume":"93","author":"Nagata","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612471164600_B34","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/0016-5085(90)90276-7","article-title":"Transferrin receptor distribution and regulation in the rat small intestine. Effect of iron stores and erythropoiesis.","volume":"98","author":"Anderson","year":"1990","journal-title":"Gastroenterology"},{"key":"2020071612471164600_B35","doi-asserted-by":"crossref","first-page":"G931","DOI":"10.1152\/ajpgi.2001.281.4.G931","article-title":"Cloning and gastrointestinal expression of rat hephaestin: relationship to other iron transport proteins.","volume":"281","author":"Frazer","year":"2001","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2020071612471164600_B36","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1136\/vr.116.16.431","article-title":"Guidelines on the recognition of pain, distress and discomfort in experimental animals and an hypothesis for assessment.","volume":"116","author":"Morton","year":"1985","journal-title":"Vet Rec"},{"key":"2020071612471164600_B37","first-page":"9","article-title":"A simple technique for measuring storage iron concentrations in formalinised liver samples.","volume":"33","author":"Torrance","year":"1968","journal-title":"S Afr J Med Sci"},{"key":"2020071612471164600_B38","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1182\/blood-2003-01-0283","article-title":"Transgenic mice overexpressing erythropoietin adapt to excessive erythrocytosis by regulating blood viscosity.","volume":"102","author":"Vogel","year":"2003","journal-title":"Blood"},{"key":"2020071612471164600_B39","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1172\/JCI112796","article-title":"Human recombinant erythropoietin promotes differentiation of murine megakaryocytes in vitro.","volume":"79","author":"Ishibashi","year":"1987","journal-title":"J Clin Invest"},{"key":"2020071612471164600_B40","first-page":"1028","article-title":"Human erythropoietin stimulates murine megakaryopoiesis in serum-free culture.","volume":"15","author":"Sakaguchi","year":"1987","journal-title":"Exp Hematol"},{"key":"2020071612471164600_B41","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1182\/blood.V88.3.803.803","article-title":"Low levels of erythroid and myeloid progenitors in thrombopoietin-and c-mpl-deficient mice.","volume":"88","author":"Carver-Moore","year":"1996","journal-title":"Blood"},{"key":"2020071612471164600_B42","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1681\/ASN.V3101672","article-title":"Effect of recombinant human erythropoietin on platelet production in dialysis patients.","volume":"3","author":"Kaupke","year":"1993","journal-title":"J Am Soc Nephrol"},{"key":"2020071612471164600_B43","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0167-0115(97)00025-6","article-title":"Effect of cholecystokinin and gastrin on human peripheral blood lymphocyte functions, implication of cyclic AMP and interleukin 2.","volume":"70","author":"Carrasco","year":"1997","journal-title":"Regul Pept"},{"key":"2020071612471164600_B44","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0196-9781(95)02133-7","article-title":"Modulation of murine peritoneal macrophage functions by gastrin.","volume":"17","author":"de la Fuente","year":"1996","journal-title":"Peptides"},{"key":"2020071612471164600_B45","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1096\/fj.05-5696fje","article-title":"Gastrin induces leukocyte-endothelial cell interactions in vivo and contributes to the inflammation caused by Helicobacter pylori.","volume":"20","author":"Alvarez","year":"2006","journal-title":"FASEB J"},{"key":"2020071612471164600_B46","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0196-9781(91)90184-Q","article-title":"Visualization of cholecystokinin receptors on a subset of human monocytes and in rat spleen.","volume":"12","author":"Sacerdote","year":"1991","journal-title":"Peptides"},{"key":"2020071612471164600_B47","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1182\/blood.V88.7.2683.bloodjournal8872683","article-title":"Autocrine loop through cholecystokinin-B\/gastrin receptors involved in growth of human leukemia cells.","volume":"88","author":"Iwata","year":"1996","journal-title":"Blood"},{"key":"2020071612471164600_B48","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S0024-3205(97)00414-1","article-title":"mRNAs encoding CCKB but not CCKA receptors are expressed in human T lymphocytes and Jurkat lymphoblastoid cells.","volume":"61","author":"Cuq","year":"1997","journal-title":"Life Sci"},{"key":"2020071612471164600_B49","doi-asserted-by":"crossref","first-page":"7593","DOI":"10.1073\/pnas.91.16.7593","article-title":"Antiproliferative gastrin\/cholecystokinin receptor antagonists target the 78-kDa gastrin-binding protein.","volume":"91","author":"Baldwin","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612471164600_B50","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/sj.onc.1209798","article-title":"Annexin II binds progastrin and gastrin-like peptides, and mediates growth factor effects of autocrine and exogenous gastrins on colon cancer and intestinal epithelial cells.","volume":"26","author":"Singh","year":"2007","journal-title":"Oncogene"},{"key":"2020071612471164600_B51","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nm.1963","article-title":"Impaired gastric acidification negatively affects calcium homeostasis and bone mass.","volume":"15","author":"Schinke","year":"2009","journal-title":"Nat Med"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/152\/8\/3062\/9038577\/endo3062.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/152\/8\/3062\/9038577\/endo3062.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T07:33:08Z","timestamp":1686123188000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/152\/8\/3062\/2457235"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,6,7]]},"references-count":51,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2011,8,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2010-1474","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,6,7]]}}}