Erythropoietin (EPO)
Also known as: EPO, epoetin
A glycoprotein produced mainly by renal peritubular interstitial fibroblasts in response to tissue hypoxia that stimulates red-cell production in the bone marrow.
Overview
About 90 % of EPO in adults is made by peritubular interstitial fibroblast-like cells in the renal cortex and outer medulla (≈10 % by hepatocytes, which are the main source in the fetus). The kidney is an ideal oxygen sensor because its O₂ consumption tracks its blood flow, so local P_O₂ reflects arterial O₂ content.
Oxygen sensing uses the hypoxia-inducible factor (HIF) pathway: in normoxia, prolyl hydroxylases tag HIF-α subunits for destruction via the von Hippel–Lindau protein; in hypoxia HIF-2α escapes, binds HIF-β and activates EPO gene transcription — EPO can rise hundreds-fold within hours. EPO binds the EPO receptor, a cytokine receptor using JAK2–STAT5, on CFU-E and proerythroblasts in the bone marrow, preventing their apoptosis and stimulating proliferation and differentiation; reticulocytes increase within 3–4 days and haemoglobin over weeks.
- Location
Source: renal peritubular interstitial fibroblasts (≈90 %); liver (≈10 %). Target: erythroid progenitors (CFU-E, proerythroblasts) in red bone marrow.
Function
- Stimulates erythropoiesis to match oxygen-carrying capacity to tissue needs.
- Physiology
Class: glycoprotein (165 aa, ≈30 kDa). Receptor: EPO receptor — JAK2/STAT5. Half-life ≈5–9 h (IV).
- Regulation
Stimulated by renal hypoxia — anaemia, low arterial P_O₂ (altitude, lung disease), increased haemoglobin O₂ affinity; androgens increase it. Rising red-cell mass closes the loop.
Clinical significance
Anaemia of chronic kidney disease
Loss of EPO-producing cells causes normocytic anaemia; treated with erythropoiesis-stimulating agents (epoetin, darbepoetin; risks: hypertension, thrombosis, pure red-cell aplasia) or oral HIF-prolyl hydroxylase inhibitors (roxadustat, daprodustat), after correcting iron deficiency.
Polycythaemia
Appropriate secondary polycythaemia (high EPO): altitude, COPD, sleep apnoea, cyanotic heart disease, smoking. Inappropriate (EPO-secreting tumours): renal cell carcinoma, hepatocellular carcinoma, cerebellar haemangioblastoma, uterine fibroids. Polycythaemia vera (JAK2 V617F) has low EPO. EPO misuse in endurance sport causes hyperviscosity and thrombosis.
Compiled from standard anatomy and physiology references — see the Endocrine System sources. For education only; not medical advice.