Erythropoietin
Erythropoietin (EPO) is a hormone produced by the kidney. It functions to regulate red blood cell production (erythropoiesis) in the bone marrow.
- functions
- regulation of expression
- consequences of overexpression
- consequences of underexpression
- signalling pathways
- structure
Function
EPO production increases in states of decreased tissue oxygen delivery.
EPO travels to the marrow, where it binds to EPO receptors on committed RBC precursors. Within hours, there is a noticable increase in DNA synthesis, followed by proliferation and differentiation. The full marrow response takes several days, with a detectable increase in hematocrit taking a week or more.
Regulation of Expression
EPO is expressed by peritubular interstitial cells in the kidney cortex.
EPO expression is increased by a decrease in Hb oxygenation (high altitudes, pulmonary dysfunction), hemoglobin level (anemia), or hemoglobin affinity for oxygen (shift in oxygen dissociation curve).
EPO expression increases logarithmically once levels fall below 120 g/L.
EPO levels are decreased by inflammatory cytokines such as TNF-a and TGFb.
Drugs such as chemotherapy, cyclosporin A, and theophylline decrease EPO production.
Consequences of Overexpression
Consequences of Underexpression
Renal failure causes a drop in erythropoietin, leading to anemia.
Signalling Pathways
EPO transcription is regulated by HIF-1
Structure
EPO is a highly glycosylated, 39 kDa protein.