title: Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin.
abstract: Expression of hepcidin, the key hormone governing iron transport, is reduced by anemia in a manner which appears dependent on increased bone marrow activity. The temporal associations between plasma hepcidin and other iron parameters were examined in healthy humans after erythropoietin administration and venesection. Profound hepcidin suppression appeared abruptly 24 hours after subcutaneous erythropoietin (P=0.003), and was near maximal at onset, with peak (mid-afternoon) levels reduced by 73.2%, gradually recovering over the following two weeks. Minor changes in circulating iron, soluble transferrin receptor and growth differentiation factor-15 were observed after the reduction in hepcidin. Similar but more gradual changes in these parameters were observed after reducing hematocrit by removal of 250 mL blood. These human studies confirm the importance of a rapidly responsive marrow-hepcidin axis in regulating iron supply in vivo, and suggest that this axis is regulated by factors other than circulating iron, soluble transferrin receptor or growth differentiation factor-15.
authors.affiliation: Renal Medicine, Imperial College London, Commonwealth Building, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK. d.ashby@imperial.ac.uk
authors.forename: Damien R
authors.initials: DR
authors.lastname: Ashby
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Gale
authors.forename: Mark
authors.initials: M
authors.lastname: Busbridge
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Murphy
authors.forename: Neill D
authors.initials: ND
authors.lastname: Duncan
authors.forename: Tom D
authors.initials: TD
authors.lastname: Cairns
authors.forename: David H
authors.initials: DH
authors.lastname: Taube
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
authors.forename: Frederick W K
authors.initials: FW
authors.lastname: Tam
authors.forename: Richard
authors.initials: R
authors.lastname: Chapman
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Maxwell
authors.forename: Peter
authors.initials: P
authors.lastname: Choi
mesh_terms: D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism*; D004921:Erythropoietin / Q000008:administration & dosage*; D055436:Growth Differentiation Factor 15 / Q000378:metabolism; D064451:Hepcidins; D006801:Humans; D007279:Injections, Subcutaneous; D007501:Iron / Q000378:metabolism*; D008297:Male; D011990:Receptors, Transferrin / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D055436:Growth Differentiation Factor 15; C578702:HAMP protein, human; D064451:Hepcidins; D011990:Receptors, Transferrin; D014168:Transferrin; D004921:Erythropoietin; D007501:Iron