Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital

Induction of erythroferrone in healthy humans by micro-dose recombinant erythropoietin or high-altitude exposure

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Intravascular volumes evaluated by a carbon monoxide rebreathing method in patients undergoing chronic hemodialysis

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Did you know-why does maximal oxygen uptake increase in humans following endurance exercise training?

    Research output: Contribution to journalEditorialResearchpeer-review

  3. Transcerebral exchange kinetics of large neutral amino acids during acute inspiratory hypoxia in humans

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. The role of blood volume in cardiac dysfunction and reduced exercise tolerance in patients with diabetes

    Research output: Contribution to journalReviewResearchpeer-review

  5. Age-dependent impairment of the erythropoietin response to reduced central venous pressure in HFpEF patients

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Paul Robach
  • Elena Gammella
  • Stefania Recalcati
  • Domenico Girelli
  • Annalisa Castagna
  • Matthieu Roustit
  • Carsten Lundby
  • Anne-Kristine Lundby
  • Pierre Bouzat
  • Samuel Vergès
  • Guillaume Séchaud
  • Pierluigi Banco
  • Mario Uhr
  • Catherine Cornu
  • Pierre Sallet
  • Gaetano Cairo
View graph of relations

The erythropoietin (Epo)-erythroferrone (ERFE)-hepcidin axis coordinates erythropoiesis and iron homeostasis. While mouse studies have established that Epo-induced ERFE production represses hepcidin synthesis by inhibiting hepatic BMP/SMAD signaling, evidence for the role of ERFE in humans is limited. To investigate the role of ERFE as a physiological erythroid regulator in humans, we conducted two studies: first, 24 males received six injections of saline (placebo), recombinant Epo (rhEpo) 20 UI kg-1 (micro-dose) or 50 UI kg-1 (low-dose). Second, we quantified ERFE in 22 subjects exposed to high altitude (3800 m) for 15 hours. In the first study, total hemoglobin mass (Hbmass) increased after low- but not after micro-dose injections, when compared to placebo. Serum ERFE levels were enhanced by rhEpo, remaining higher than after placebo for 48 (micro-dose) or 72 hours (low-dose) post-injections. Conversely, hepcidin levels decreased when Epo and ERFE arose, before any changes in serum iron parameters occurred. In the second study, serum Epo and ERFE increased at high altitude. The present results demonstrate that in healthy humans ERFE responds to slightly increased Epo levels not associated with Hbmass expansion and down-regulates hepcidin in an apparently iron-independent way. Notably, ERFE flags micro-dose Epo, thus holding promise as novel anti-doping biomarker.

Original languageEnglish
Issue number2
Pages (from-to)384-390
Number of pages7
Publication statusPublished - 1 Feb 2021

ID: 61782012