Hepcidin: from discovery to differential diagnosis.
Although iron is essential for living organisms to survive, its reactive properties require strict regulation in order to prevent toxic effects. Hepcidin, a liver produced peptide hormone, is thought to be the central regulator of body iron metabolism. Its production is mainly controlled by the erythropoietic activity of the bone-marrow, the amount of circulating and stored body iron, and inflammation. Recent reports, however, provide new hypotheses on how hepcidin might exert its regulatory function. Although hepcidin was first discovered in human urine and serum, most of our understanding of hepcidin regulation and action comes from in vitro and mice studies that often use hepcidin mRNA expression as a read out. The difficulties in carrying out studies in humans have mostly been due to the lack of suitable hepcidin assay. The recent development of assays to measure hepcidin in serum and urine has offered new opportunities to study hepcidin regulation in humans. However, for the moment, only a small number of laboratories are able to perform these assays. The aim of this review is to discuss insights into hepcidin regulation obtained from recent clinical studies in the light of findings from in vitro and mice studies. Ongoing studies in humans should provide us with more information on the etiology of iron metabolism disorders in order to create new therapeutic strategies and improve differential diagnosis protocols for these diseases.
Kemna
Erwin H J M
EH
Department of Clinical Chemistry, Radboud University Nijmegen Medical Centre, P.O. Box 9101 6500 HB Nijmegen, The Netherlands.
Tjalsma
Harold
H
Willems
Hans L
HL
Swinkels
Dorine W
DW
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000097:blood* / Q000378:metabolism* / Q000652:urine*; D001774:Blood Chemical Analysis / Q000379:methods; D002624:Chemistry, Clinical / Q000379:methods; D005786:Gene Expression Regulation; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019189:Iron Metabolism Disorders / Q000175:diagnosis / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008954:Models, Biological; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D016482:Urinalysis / Q000379:methods
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D064451:Hepcidins; D012333:RNA, Messenger; D007501:Iron