title: Early effects of erythropoietin on serum hepcidin and serum iron bioavailability in healthy volunteers.
abstract: Hepcidin regulates plasma iron bioavailability and subsequently iron availability for erythropoiesis. rHuEPO has been reported to decrease hepcidin expression in case of repeated subcutaneous injections. Thus, hepcidin level measurement could be a candidate marker for detection of rHuEPO abuse. However, when used for doping, rHuEPO can be injected intravenously and the scheme of injection is unknown. Our aim was to evaluate the early effects of a single intravenous rHuEPO injection on serum hepcidin levels. Fourteen male healthy volunteers received one intravenous injection of 50 U/Kg of rHuEPO during a placebo-controlled, randomized, double-blind, cross-over study. Serum hepcidin, quantified by a competitive ELISA method and iron parameters was then evaluated for 24 h. Serum levels of hepcidin were significantly increased 4 h after rHuEPO injection when compared with placebo injection (78.3 ± 55.5 vs. 57.5 ± 34.6 ng/ml, respectively; +36%, p < 0.05), whereas iron and transferrin saturation dramatically decreased 12 h after rHuEPO injection when compared with placebo injection (9.2 ± 3.5 vs. 15.8 ± 4.2 μg/l, respectively; -42%, p < 0.05 and 14.8 ± 5.0 vs. 26.3 ± 6.4%, respectively; -44%, p < 0.05). In addition, 12 and 24 h after rHuEPO injection serum hepcidin levels were lower compared with placebo injection (41.6 ± 27.4 vs. 56.6 ± 28.1 ng/ml after 12 h; -27%, p < 0.05 and 26.0 ± 29.6 vs. 81.2 ± 29.4 ng/ml after 24 h; -68%, p < 0.05). Intravenous injection of recombinant EPO induces a precocious and transient increase of serum hepcidin leading to a transient decrease of iron bioavailability. The transitory increase and dynamics of its concentration make difficult the practical use of hepcidin to detect rHuEPO doping.
authors.affiliation: INSERM, Centre d'investigation Clinique 0203, 35033 Rennes, France. fabrice.laine@chu-rennes.fr
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lainé
authors.forename: Bruno
authors.initials: B
authors.lastname: Laviolle
authors.forename: Martine
authors.initials: M
authors.lastname: Ropert
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bouguen
authors.forename: Jeff
authors.initials: J
authors.lastname: Morcet
authors.forename: Catherine
authors.initials: C
authors.lastname: Hamon
authors.forename: Catherine
authors.initials: C
authors.lastname: Massart
authors.forename: Mark
authors.initials: M
authors.lastname: Westermann
authors.forename: Yves
authors.initials: Y
authors.lastname: Deugnier
authors.forename: Olivier
authors.initials: O
authors.lastname: Loréal
mesh_terms: D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D001682:Biological Availability; D018592:Cross-Over Studies; D004300:Doping in Sports; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000008:administration & dosage*; D005293:Ferritins / Q000097:blood; D005602:France; D055436:Growth Differentiation Factor 15 / Q000097:blood; D006397:Hematinics / Q000008:administration & dosage*; D064451:Hepcidins; D006801:Humans; D007275:Injections, Intravenous; D007501:Iron / Q000097:blood*; D033862:Iron-Binding Proteins / Q000097:blood; D008297:Male; D010919:Placebos; D011956:Receptors, Cell Surface / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage; D015813:Substance Abuse Detection; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism; D055815:Young Adult
chemical_list: D023181:Antimicrobial Cationic Peptides; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; C578702:HAMP protein, human; D006397:Hematinics; D064451:Hepcidins; D033862:Iron-Binding Proteins; D010919:Placebos; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D014168:Transferrin; C103998:epoetin beta; C027293:ferritin receptor; D004921:Erythropoietin; D005293:Ferritins; D007501:Iron