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. 2010 Mar;95(3):505-8.
doi: 10.3324/haematol.2009.013136. Epub 2009 Oct 14.

Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin

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Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin

Damien R Ashby et al. Haematologica. 2010 Mar.

Abstract

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.

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Figures

Figure 1.
Figure 1.
Effect of erythropoietin administration on plasma hepcidin and related parameters. Healthy controls (n=6) received subcutaneous erythropoietin at 09:00 on the second day. Levels of plasma hepcidin (A), transferrin saturation (B), ferritin (C), erythropoietin (D), GDF15 (E) and sTFR (F) are shown throughout the week (mean±se). GDF15: growth differentiation factor-15, sTFR: soluble transferrin receptor.
Figure 2.
Figure 2.
Effect of venesection on plasma hepcidin and related parameters. In healthy controls (n=6) hematocrit was acutely reduced by venesection (250ml) at 09:00 on the second day. Levels of plasma hepcidin (A), transferrin saturation (B), ferritin (C), erythropoietin (D), GDF15 (E) and sTFR (F) are shown throughout the week (mean±se). GDF15: growth differentiation factor-15, sTFR: soluble transferrin receptor.

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