The Physiology of Erythropoietin, Medical Application, and Abuse in Sport


Erythropoietin, a 34-kDa glycoprotein, is an essential hormone for the induction of erythropoiesis. Pri- marily occurring in the renal cortex, hepatocytes also contribute to erythropoietin synthesis. The 165 amino acid chain consists of four ?-helices, two ?-pleated sheets and two disulphide bridges. Unable to be stored in the body, erythropoietin is under constant regulation by partial pressure of oxygen, haemoglobin -O2 affinity and -concentration, in a negative feedback loop. In hypoxic conditions, hypoxia-inducible transcription factors promote the expression of the erythropoietin gene, allowing renal erythropoietin producing cells to transition from OFF-REP to ON-REP. When activated, ON- REPs produce erythropoietin, which binds to erythropoietin-specific receptors in the bone marrow, where it encourages differentiation and proliferation of haematopoietic stem cells. A variety of medical conditions result in anaemia, including iron deficiency, chronic kidney disease and anaemia of chronic disease. Renal fibrosis and chemotherapy for cancer patients also cause anaemia because renal cells are consequently destroyed. Anaemic patients can be treated with erythropoietin stimulating agents such as human recombinant erythropoietin; however, this treatment cannot completely replace blood transfusions. In professional sports, erythropoietin has been abused as a performance enhancer, in- creasing haemoglobin count, and thus stamina and overall performance. In recent years, erythropoietin has demonstrated potential for tumour cell marking, possibly opening a door to a new type of cancer treatment.





Publication date

August 2021


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