title: Kidney-synthesized erythropoietin is the main source for the hypoxia-induced increase in plasma erythropoietin in adult humans.
abstract: OBJECTIVE
  Erythropoietin (EPO) is mainly synthesized within renal peritubular fibroblasts, and also other tissues such as the liver possess the ability. However, to what extent non-kidney produced EPO contributes to the hypoxia-induced increase in circulating EPO in adult humans remains unclear.
  
  
  METHODS
  We aimed to quantify this by assessing the distribution of EPO glycoforms which are characterized by posttranslational glycosylation patterns specific to the synthesizing cell. The analysis was performed on samples obtained in seven healthy volunteers before, during and after 1 month of sojourn at 3,454 m altitude.
  
  
  RESULTS
  Umbilical cord (UC) plasma served as control. As expected a peak (p < 0.05) in urine (2.3 ± 0.5-fold) and plasma (3.3 ± 0.5-fold) EPO was observed on day 1 of high-altitude exposure, and thereafter the concentration decreased for the urine sample obtained after 26 days at altitude, but remained elevated (p < 0.05) by 1.5 ± 0.2-fold above the initial sea level value for the plasma sample. The EPO glycoform heterogeneity, in the urine samples collected at altitude, did not differ from values at sea level, but were markedly lower (p < 0.05) than the mean percent migrated isoform (PMI) for the umbilical cord samples.
  
  
  CONCLUSIONS
  Our studies demonstrate (1) UC samples express a different glycoform distribution as compared to adult humans and hence illustrates the ability to synthesis EPO in non-kidney cells during fetal development (2) as expected hypoxia augments circulating EPO in adults and the predominant source here for remains being kidney derived.
authors: Center for Integrative Human Physiology, Institute of Physiology, University of Zürich, Winterthurerstrasse 190, 8057, Zürich, Switzerland.
authors: Anne-Kristine Meinild
authors: AK
authors: Lundby
authors: Stefanie
authors: S
authors: Keiser
authors: Christoph
authors: C
authors: Siebenmann
authors: Leonhard
authors: L
authors: Schäffer
authors: Carsten
authors: C
authors: Lundby
mesh_terms: D000328:Adult; D000531:Altitude; D016022:Case-Control Studies; D004921:Erythropoietin / Q000097:blood* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D000860:Hypoxia / Q000097:blood* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D011499:Protein Processing, Post-Translational
chemical_list: D004921:Erythropoietin