Erythropoietin (or EPO) is a glycoprotein hormone It is a growth factor hormone for erythrocyte (red blood cell) precursors in the bone marrow. It increases the number of red blood cells in the blood. Synthetic erythropoietin is available as an expensive injectable therapeutic agent produced by recombinant DNA technology.

Production

Most erythropoietin is produced in the human renal cortex. It has been found that it is also produced in the liver (mainly in the fetus), the brain and uterus. Erythropoietin production is stimulated by the reduction of oxygen in the renal arteries.

Action

Like other protein hormones, erythropoietin acts by binding to a specific erythropoietin receptor (EpoR) embedded in the plasma membrane of target cells, the red cell precursors in the bone marrow. Erythropoietin stimulates stem cells in the bone marrow to transform into erythrocytes (red blood cells). This increases the number of circulating red blood cells. It is reflected as increases of the hematocrit, hemoglobin, and RBC counts in a CBC).

The role of paracrine erythropoietin in the brain and uterus is not fully elucidated. However, in several animal models of stroke and inflammatory disease EPO provides neuroprotection, presumably not by improving oxygen delivery, but by activation of anti-apoptotic and anti-oxidative pathways.

Deficiency of erythropoietin

Because the kidneys are the primary source of erythropoietin, chronic renal failue often results in deficiency, and consequently a hypoplastic anemia. Synthetic erythropoietin was originally developed primarily for this use.

Erthyropoietin as a therapeutic agent

Administered erythropoietin produces the same effect as a transfusion of red blood cells, but can be given chronically without the risks of repeated transfusions. It is most often given to people with anemia associated with chronic renal failure, but can be beneficial in many types of anemia due to diseases that interfere with RBC production, such as that due to cancer chemotherapy. Epogen and Procrit are 2 US brands; at least one has been advertised on television as a treatment for tiredness in cancer patients.

The gene which encodes Erythropoietin production was cloned in 1985 and has been successfully implanted in guinea pigs in order to produce artificial Erythropoietin in the form of Epoetin.

There are differences between human erythropoietin and the erythropoietin of the pig. Because of this difference there are concerns that xenotransplants of pig kidneys into humans may lead to a lack of red blood cells in the recipient.

Another substance in the same class is darbepoetin.

Erythropoietin as a doping agent

EPO has been extensively used as an ergogenic aid, a doping drug, in some sports, particularly cycling and long-distance running, because higher amounts of red blood cells can increase the oxygen carrying capacity of the blood and improve endurance. (See Tour de France.)