title: Serum hepcidin levels and muscle iron proteins in humans injected with low- or high-dose erythropoietin.
abstract: Inhibition of hepcidin expression by erythropoietic signals is of great physiological importance; however, the inhibitory pathways remain poorly understood. To investigate (i) the direct effect of erythropoietin (Epo) and (ii) the contribution of putative mediators on hepcidin repression, healthy volunteers were injected with a single dose of Epo, either low (63 IU/kg, n = 8) or high (400 IU/kg, n = 6). Low-dose Epo provoked hepcidin down-modulation within 24 h; the effect was not immediate as hepcidin circadian variations were still present following injection. High-dose Epo induced no additional effect on the hepcidin response, that is hepcidin diurnal fluctuations were not abolished in spite of extremely high Epo levels. We did not find significant changes in putative mediators of hepcidin repression, such as transferrin saturation, soluble transferrin receptor, or growth differentiation factor 15. Furthermore, the potential hepcidin inhibitor, soluble hemojuvelin, was found unaltered by Epo stimulation. This finding was consistent with the absence of signs of iron deficiency observed at the level of skeletal muscle tissue. Our data suggest that hepcidin repression by erythropoietic signals in humans may not be controlled directly by Epo, but mediated by a still undefined factor.
authors.affiliation: Département médical, Ecole Nationale de Ski et d'Alpinisme, site de l'Ecole Nationale des Sports de Montagne, Chamonix, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Robach
authors.forename: Stefania
authors.initials: S
authors.lastname: Recalcati
authors.forename: Domenico
authors.initials: D
authors.lastname: Girelli
authors.forename: Natascia
authors.initials: N
authors.lastname: Campostrini
authors.forename: Tibor
authors.initials: T
authors.lastname: Kempf
authors.forename: Kai C
authors.initials: KC
authors.lastname: Wollert
authors.forename: Michela
authors.initials: M
authors.lastname: Corbella
authors.forename: Paolo
authors.initials: P
authors.lastname: Santambrogio
authors.forename: Luigi
authors.initials: L
authors.lastname: Perbellini
authors.forename: Carole
authors.initials: C
authors.lastname: Brasse-Lagnel
authors.forename: Britt
authors.initials: B
authors.lastname: Christensen
authors.forename: Stéphane
authors.initials: S
authors.lastname: Moutereau
authors.forename: Carsten
authors.initials: C
authors.lastname: Lundby
authors.forename: Gaetano
authors.initials: G
authors.lastname: Cairo
mesh_terms: D000328:Adult; D001706:Biopsy; D002097:C-Reactive Protein / Q000378:metabolism; D018592:Cross-Over Studies; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000494:pharmacology*; D058851:GPI-Linked Proteins / Q000378:metabolism*; D055436:Growth Differentiation Factor 15 / Q000378:metabolism; D000071020:Hemochromatosis Protein; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D007501:Iron / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D016037:Single-Blind Method; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism; D055815:Young Adult
chemical_list: C526140:GDF15 protein, human; D058851:GPI-Linked Proteins; D055436:Growth Differentiation Factor 15; C481006:HJV protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D009124:Muscle Proteins; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; D014168:Transferrin; D004921:Erythropoietin; D000068817:Epoetin Alfa; D002097:C-Reactive Protein; D007501:Iron