Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin.
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.
Ashby
Damien R
DR
Renal Medicine, Imperial College London, Commonwealth Building, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK. d.ashby@imperial.ac.uk
Gale
Daniel P
DP
Busbridge
Mark
M
Murphy
Kevin G
KG
Duncan
Neill D
ND
Cairns
Tom D
TD
Taube
David H
DH
Bloom
Stephen R
SR
Tam
Frederick W K
FW
Chapman
Richard
R
Maxwell
Patrick H
PH
Choi
Peter
P
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
D023181:Antimicrobial Cationic Peptides; D055436:Growth Differentiation Factor 15; C578702:HAMP protein, human; D064451:Hepcidins; D011990:Receptors, Transferrin; D014168:Transferrin; D004921:Erythropoietin; D007501:Iron