Short of oxygen, your kidneys can boost one hormone a thousandfold
Your kidneys constantly monitor how much oxygen reaches them. When supplies run low, they ramp up a hormone called erythropoietin, sometimes a thousandfold, ordering the bone marrow to build more red blood cells. Medicine turned that signal into a drug for anaemia, and some athletes turned it into a way to cheat.
Erythropoietin, or EPO, is a glycoprotein hormone, heavily coated in sugars that make up about 40 percent of its weight. In adults roughly 90 percent is made by fibroblast-like cells deep in the kidney's cortex, near the tiny blood vessels that surround its tubules; the liver supplies the rest and is the main source before and just after birth. At rest, blood carries only about 10 mU/mL. Under oxygen stress, from anaemia or chronic lung disease, levels can reach 10,000 mU/mL. Once released it lasts around five hours in the bloodstream.
The control switch is elegant. Cells constantly make proteins called hypoxia-inducible factors, but when oxygen and iron are plentiful those proteins are tagged and destroyed. When oxygen falls they survive and drive EPO production, while a second brake, GATA2, eases off. EPO then docks on receptors of early red cell precursors in the marrow, triggering a JAK2 signalling cascade that keeps those cells alive, dividing and maturing. One precursor stage depends on it completely; without EPO, normal red cell production does not happen.
Claims that EPO also protects the heart, nerves and kidneys after injury have been popular but remain contested. Many studies found no effect, the relevant tissues carry few receptors, and human trials have not reproduced the benefits seen in animals.
Recombinant versions, such as epoetin alfa and beta, are grown in cell culture and used for anaemia caused by chronic kidney disease, myelodysplasia or chemotherapy. They carry serious risks, including heart attack, stroke, blood clots and tumour recurrence, especially if haemoglobin is pushed above about 11 to 12 g/dL. Their illicit use in sport can often be caught because the manufactured protein differs slightly from the body's own in how it is modified after being made.
Source: Erythropoietin
