Erythropoietin (EPO)

Updated: Oct 7, 2021


 

Erythropoietin (EPO) is a cytokine glycoprotein hormone, the main regulator of erythropoiesis, which stimulates the formation of erythrocytes from late progenitor cells (it binds to erythropoietin-sensitive receptors, which are mainly located on erythroblasts, and promotes the active proliferation of blast forms) and increases the release of reticulocytes from the bone marrow.


The production of erythropoietin is regulated at the level of transcription of its gene, and since the only physiological stimulus increasing the number of cells synthesizing erythropoietin is hypoxia, the production and metabolism of erythropoietin does not depend on its concentration in plasma. Approximately 90% of erythropoietin is synthesized in the cells of the capillaries of the renal glomeruli and up to 10% produce liver cells.


In recent years, it has been established that in small quantities erythropoietin is synthesized by astrocytes of the nervous tissue, where it performs a neuroprotective role in hypoxic and ischemic brain lesions.


Erythropoietin is an extremely active hormone that exerts its action in the body in picomolar concentrations. Small fluctuations of its concentration in the blood lead to significant changes in the rate of erythropoiesis, and the normal range of its concentration ranges from 4 to 26 IU / l. Therefore, until the hemoglobin concentration falls below 105 g / l, the concentration of erythropoietin does not exceed the specified range and it is almost impossible to identify its increase. Erythrocytosis leads to the suppression of the production of erythropoietin by the mechanism of negative feedback. The half-life of erythropoietin is 69 hours.

Thus, knowing the mechanism of action of erythropoietin, one can consider its use as doping.

Erythropoietin belongs to the group S2 - peptide hormones (the list of prohibited substances and methods). The expediency of its use lies in the fact that it can cause an increase in the number of red blood cells in the blood and increase the oxygen capacity of the blood. Accordingly, more oxygen can be delivered to the tissues (especially muscle tissue!), Which increases the efficiency of the body.


The active use of erythropoietin doping originates from the moment when it was possible to obtain it artificially. By the mid-1980s, the first recombinant erythropoietin was obtained by introducing the human EPO gene (localized in humans on the seventh chromosome in the 11q-12q region) into ovarian hamsters.

Recombinant human p-EPO (obtained by genetic engineering) Recormon is identical in amino acid composition to natural human EPO. However, there are minor differences in the composition of glycosidic residues that affect the physico-chemical properties of the entire hormone molecule.


Since 1988, alpha-EPO (Eralfon, Binocrit, Eprex) and beta-EPO (Vero epoetin, Erythropoietin (Binnopharm), Epostim) have been used. When subcutaneously, their bioavailability is about 25%, the maximum concentration in the blood - after 12-18 hours, the half-life - up to 24 hours (with intravenous administr