MadSci Network: Medicine

Re: Whats parts of the red blood cell are affected by the drug EPO?

Date: Wed Dec 27 15:50:56 2000
Posted By: Ingrid Dodge, Grad student, Immunology
Area of science: Medicine
ID: 971453534.Me

Dear Waqas:

Hello. This is an interesting question. As you mentioned in your question, EPO, or erythropoietin, is taken to increase red blood cell production. The hormone erythropoietin is normally produced by the kidney peritubular capillary epithelium in adults, and by the liver and kidney in newborns, in response to low oxygen tension in the blood. Once EPO is released, it travels through the bloodstream to the bone marrow, where it binds to the EPO receptor on erythroid progenitor cells, causing them to proliferate and differentiate into mature red blood cells, which lack a nucleus. This increase in red blood cells allows for greater oxygen carrying capacity in the blood, but it also increases the viscosity of the blood, leading to concerns that overuse of erythropoietin could lead to increased risk of blood clots, although this has not been proven.

Some people naturally have mutations in their erythropoietin receptors, rendering them especially sensitive to epo (some of these people have even been olympic cross country competitors), and thus they naturally have a high level of red blood cells, and consequently a high hematocrit. Erythropoietin has been used effectively in the treatment of anemia due to chemotherapeutic therapy for cancer or AZT treament for AIDS. The red blood cells that are formed as a result of recombinant EPO administration are no different from the red blood cells generated by natural EPO. There simply are more red blood cells around. EPO doping by athletic competitors can be detected, however, as the recombinant EPO has a different sugar pattern on the protein than endogenously produced EPO, and that sugar difference can be detected in the competitor's urine. So for an athlete to increase their EPO production legally, the only choice is to train at altitude, where the low oxygen content in the air spurs the body to make its own EPO.

I hope this has answered your question!
Ingrid Dodge
Mad Scientist

Reference about mutant epo receptors:
Livnah O, Stura EA, Middleton SA, Johnson DL, Jolliffe LK, Wilson IA. 1999. Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation. Science 283: 987-990.

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