n/an/an/an/anan/an/an/an/an/aErythropoietin (/ɪˌrɪθroʊˈpɔɪ.ɪtɪn, -rə-, -pɔɪˈɛtɪn, -ˈiːtɪn/;[1][2][3] EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bone marrow.

Low levels of EPO (around 10 mU/mL) are constantly secreted in sufficient quantities to compensate for normal red blood cell turnover.

Erythropoietin is produced by interstitial fibroblasts in the kidney in close association with the peritubular capillary and proximal convoluted tubule.

Risks of therapy include death, myocardial infarction, stroke, venous thromboembolism, and tumor recurrence.

[4] It can often be detected in blood, due to slight differences from the endogenous protein; for example, in features of posttranslational modification.

Under hypoxic conditions, the kidney will produce and secrete erythropoietin to increase the production of red blood cells by targeting CFU-E, proerythroblast and basophilic erythroblast subsets in the differentiation.

Precursors of red cells, the proerythroblasts and basophilic erythroblasts also express erythropoietin receptor and are therefore affected by it.

Clinical trials in humans with ischemic heart, neural and renal tissues have not demonstrated the same benefits seen in animals.

[7][8] EPO binds to the erythropoietin receptor on the red cell progenitor surface and activates a JAK2 signalling cascade.

However, indirect dependence of red cell longevity in the blood on plasma erythropoietin levels has been reported, a process termed neocytolysis.

In adults, EPO is synthesized mainly by interstitial cells in the peritubular capillary bed of the renal cortex, with additional amounts being produced in the liver,[15][16][17] and the pericytes in the brain.

[18] Regulation is believed to rely on a feedback mechanism measuring blood oxygenation and iron availability.

[28] In 1985, Lin et al isolated the human erythropoietin gene from a genomic phage library and used it to produce EPO.

Postal Service Pro Cycling Team, under the leadership of Lance Armstrong and Johan Bruyneel, ran a sophisticated doping program that lasted for many years during the late 1990s and early 2000s.

[40] In September 2023 two-time tennis major champion Simona Halep received a 4-year suspension by the International Tennis Integrity Agency for two separate violations, one concerning the level of EPO in a blood sample collected in August 2022; Halep maintained her innocence, and indicated she would appeal the ban.

Halep was later cleared to return following a successful appeal, due to findings that a contaminated supplement most likely contributed to the positive tests.