Erythropoietin

Erythropoietin is a glycoprotein hormone secreted by peritubular interstitial fibroblasts in the renal cortex, with a small contribution from the liver. Hypoxia stabilizes hypoxia-inducible factor in these cells, which switches on EPO transcription. The hormone travels to the bone marrow and binds receptors on erythroid progenitors, promoting their survival and differentiation into mature red blood cells over roughly the following week.

The result is a classic negative feedback loop. Anything that lowers oxygen delivery to the kidney — anemia, chronic hypoxemia from lung disease, high altitude, or heavy smoking — raises EPO output and expands red cell mass, which in turn restores oxygen delivery and shuts the signal off. Because the kidney is the sensor and the source, chronic kidney disease causes anemia through EPO deficiency, and recombinant erythropoietin is the standard replacement. Conversely, EPO-secreting tumors such as renal cell carcinoma, hepatocellular carcinoma, and hemangioblastoma cause secondary polycythemia.

Erythropoietin is also the prototypical blood-doping agent. Raising red cell mass increases oxygen-carrying capacity and endurance performance, which is why recombinant EPO is banned by athletic governing bodies. The practice raises hematocrit and blood viscosity, increasing the risk of thrombosis, and it is detectable through tests that distinguish recombinant from endogenous hormone.

USMLE Step 1 tests erythropoietin in renal endocrine physiology and in hematology, most often through the anemia of chronic kidney disease and through paraneoplastic polycythemia. The CSCS exam covers it in the performance-enhancing substances section as a banned hormone, and CCMA blood anatomy content introduces it as the kidney-derived signal that drives red cell production.