Erythropoietin, or EPO for short, is a hormone in the glycoprotein group. It functions as a growth factor in the production of red blood cells (erythrocytes).
What is erythropoietin?
EPO is a hormone produced in the cells of the kidneys. It is composed of 165 amino acids in total. The molecular mass is 34 kDa. Four α-helices form the secondary structure. 40 percent of the molecular mass is formed from carbohydrates. The carbohydrate portion of EPO is composed of three N-glycosidically and one O-glycosidically bound side chains. Since the hormone stimulates the formation of red blood cells, EPO belongs to the group of erythropoiesis stimulating agents (ESA). ESAs play an important role in blood formation (hematopoiesis). Erythropoietin can also be produced synthetically. The biotechnologically produced hormone is used to treat dialysis patients. In these patients, blood formation is often disturbed after kidney failure. Due to various doping cases in sports, especially in cycling, erythropoietin gained widespread public awareness.
Function, effect, and tasks
Erythropoietin is formed in the kidneys and released into the blood. Via the blood, it enters the bone marrow, where it binds to special erythropoietin receptors on the cell surface of erythroblasts. Erythroblasts are the precursor cells of red blood cells. Erythropoiesis in the bone marrow always proceeds in seven steps. First, so-called proerythroblasts arise from the multipotent myeloid stem cells in the bone marrow. Through division, the proerythroblasts give rise to macroblasts. The macroblasts in turn divide to form basophilic erythroblasts. These are also called normoblasts. The basophilic erythroblasts possess erythropoietin receptors. When EPO binds to these receptors, the erythroblasts are stimulated to divide. As a result, they differentiate into polychromatic erythroblasts. After this stage, the cells lose their ability to divide. Further maturation to orthochromatic erythroblasts then occurs in the bone marrow. Reticulocytes are formed by loss of the cell nuclei. The reticulocytes are young erythrocytes that are released from the bone marrow into the blood. Only in the blood does the final maturation into the nucleus- and organelle-less red blood cells take place. However, the function of EPO is not limited to stimulating hematopoiesis. Studies have shown that the hormone is also found in cardiac muscle cells and in various cells of the nervous system. Here it appears to influence cell division processes, the formation of new blood vessels (angiogenesis), the inhibition of apoptosis and the activation of intracellular calcium. EPO has also been detected in the hippocampus. The hippocampus is a brain region that can be severely damaged by oxygen deprivation in a short period of time. Animal studies have shown that the targeted administration of EPO increases the activity of the nerves in the hippocampus. In addition, a protective effect of the hormone has been demonstrated in cerebral infarction and oxygen deprivation in the brain.
Formation, occurrence, properties, and optimal levels
Eighty-five to 90 percent of erythropoietin is produced by the kidneys. 10 to 15 percent of the hormone is produced by hepatocytes in the liver. A small amount of synthesis also occurs in the brain, testes, spleen, uterus, and hair follicles. The biosynthesis of EPO is initiated when the oxygen content in the blood is reduced. In humans, the transcription factors required for this are located on chromosome 7 at position 7q21-7q22. In the event of an oxygen deficiency, a subunit of the so-called hypoxia-induced factor (HIF) shifts from the cell fluid into the nucleus of EPO-producing cells. There, HIF binds to a matching subunit. This leads to the formation of the heterodimer HIF-1, which in turn binds to the cAMP response element-binding protein and a specific transcription factor. Finally, a protein complex consisting of three elements results. This binds to one end of the erythropoietin gene and initiates transcription there. The finished hormone is then released directly into the blood by the producing cells and reaches the bone marrow via the bloodstream. In healthy humans, the serum concentration of EPO in the blood is between 6 and 32 mU/ ml. The plasma half-life of the hormone is between 2 and 13 hours.
Diseases and disorders
Erythropoietin deficiency can result from a loss of kidney function.As a result, too few red blood cells are formed and renal anemia develops. Almost all patients who suffer from chronic kidney disease and have a serum creatinine value of more than 4 mg/dl develop such renal anemia. Chronic renal failure is most often caused by conditions such as diabetes mellitus, hypertension, glomerulopathies, renal inflammation (due to painkiller abuse), cystic kidneys, and autoimmune diseases such as vasculitides. The extent of renal anemia is usually dependent on the severity of the underlying disease. Affected individuals have reduced performance and suffer from impaired concentration and susceptibility to infection. In addition, there are general symptoms such as fatigue, dizziness or pale skin. High blood pressure, gastrointestinal complaints, itching, menstrual disorders or impotence can also occur in the context of anemia. Overall, the quality of life of affected patients is significantly reduced. EPO formation is also inhibited by inflammatory mediators such as interleukin-1 and TNF-alpha. In this way, anemia often develops in chronic diseases. Anemia occurs with prolonged inflammatory responses. Anemia in chronic disease is normocytic and hypochromic. This means that the red blood cells are normal in size but carry too little iron. The symptoms of this form of anemia are similar to those of iron deficiency anemia. Patients suffer from pallor, fatigue, impaired concentration, susceptibility to infection, and shortness of breath.
