Production of erythropoietin, the hormone that regulates how many red blood cells are released by bone marrow, is mostly carried out in the kidneys. A small amount is also produced in the liver. Usually, production of erythropoietin increases when a person loses blood or becomes short of oxygen. A protein that senses oxygen is present in the liver and kidneys, and, when blood levels are too low, it triggers erythropoietin production. In the kidneys, erythropoietin is manufactured by cells in amongst the tiny tubes where urine is formed, and in the liver, it is synthesized by those liver cells which surround veins.
Erythropoietin, which is commonly misspelled as erithropoyetin, consists of a protein molecule with a sugar attached. This type of structure is called a glycoprotein. The process of red blood cell manufacture, which erythropoietin stimulates, is known as erythropoiesis.
Production of erythropoietin rises and falls according to the amount of red blood cells, or oxygen, present in the body. This means that hemorrhaging or traveling to a high altitude will raise production, while something which increases red blood cells, such as a blood transfusion, tends to lower the production of erythropoietin. Once it has acted to increase red blood cell levels, the blood can carry more oxygen and this switches off erythropoietin production. After production has been switched off, if red cell levels fall, the production of erythropoietin is triggered again.
When people travel to high altitudes, as less oxygen becomes available in the atmosphere, the production of erythropoietin rises steeply at first. Over the next few days, the lungs begin to work harder and the levels of oxygen in the blood increase. This causes the production of erythropoietin to fall gradually. Over the same few days, the extra blood cells created in response to the initial increase in erythropoietin help transport more oxygen to the body's tissues. As long as the person stays in the high location, the number of red cells remains higher than usual, and people who are used to living in the mountains have permanently high levels.
As well as being produced in response to low levels of oxygen, more erythropoietin is also created when people take cobalt salts. These are potentially toxic substances which raise red blood cell counts but which may also damage major organs such as the heart and increase the risk of cancer. Raised levels of the hormones that control sexual development in men can also affect the production of erythropoietin. These hormones, which are also found in women, have been found to increase the amount of erythropoietin created in and released from the bone marrow.