title: Alterations of systemic and muscle iron metabolism in human subjects treated with low-dose recombinant erythropoietin.
abstract: The high iron demand associated with enhanced erythropoiesis during high-altitude hypoxia leads to skeletal muscle iron mobilization and decrease in myoglobin protein levels. To investigate the effect of enhanced erythropoiesis on systemic and muscle iron metabolism under nonhypoxic conditions, 8 healthy volunteers were treated with recombinant erythropoietin (rhEpo) for 1 month. As expected, the treatment efficiently increased erythropoiesis and stimulated bone marrow iron use. It was also associated with a prompt and considerable decrease in urinary hepcidin and a slight transient increase in GDF-15. The increased iron use and reduced hepcidin levels suggested increased iron mobilization, but the treatment was associated with increased muscle iron and L ferritin levels. The muscle expression of transferrin receptor and ferroportin was up-regulated by rhEpo administration, whereas no appreciable change in myoglobin levels was observed, which suggests unaltered muscle oxygen homeostasis. In conclusion, under rhEpo stimulation, the changes in the expression of muscle iron proteins indicate the occurrence of skeletal muscle iron accumulation despite the remarkable hepcidin suppression that may be mediated by several factors, such as rhEpo or decreased transferrin saturation or both.
authors.affiliation: Département Médical, Ecole Nationale de Ski et d'Alpinisme, 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: Cecilia
authors.initials: C
authors.lastname: Gelfi
authors.forename: Niels J
authors.initials: NJ
authors.lastname: Aachmann-Andersen
authors.forename: Jonas J
authors.initials: JJ
authors.lastname: Thomsen
authors.forename: Anne M
authors.initials: AM
authors.lastname: Norgaard
authors.forename: Alessandra
authors.initials: A
authors.lastname: Alberghini
authors.forename: Natascia
authors.initials: N
authors.lastname: Campostrini
authors.forename: Annalisa
authors.initials: A
authors.lastname: Castagna
authors.forename: Agnese
authors.initials: A
authors.lastname: Viganò
authors.forename: Paolo
authors.initials: P
authors.lastname: Santambrogio
authors.forename: Tibor
authors.initials: T
authors.lastname: Kempf
authors.forename: Kai C
authors.initials: KC
authors.lastname: Wollert
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; D015703:Antigens, CD / Q000235:genetics; D023181:Antimicrobial Cationic Peptides / Q000032:analysis / Q000096:biosynthesis; D001706:Biopsy; D027682:Cation Transport Proteins / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D004911:Erythrocyte Volume / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009211:Myoglobin / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D011990:Receptors, Transferrin / Q000235:genetics; D011994:Recombinant Proteins; D055815:Young Adult; D000098742:Ferroportin
chemical_list: D015703:Antigens, CD; D023181:Antimicrobial Cationic Peptides; C068126:CD71 antigen; D027682:Cation Transport Proteins; C578702:HAMP protein, human; D006454:Hemoglobins; D064451:Hepcidins; D009211:Myoglobin; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; C103998:epoetin beta; D000098742:Ferroportin; D004921:Erythropoietin; D007501:Iron