Erythropoietin

Erythropoietin, briefly too EPO called, is a hormone from the group of glycoproteins. It acts as a growth factor in the production of red blood cells (erythrocytes).

What is erythropoietin?

EPO is a hormone made in the cells of the kidneys. It consists of a total of 165 amino acids. The molecular mass is 34 kDa. Four α-helices form the secondary structure. 40 percent of the molecular mass is made up of carbohydrates. The carbohydrate content of EPO is composed of three N-glycosidically and one O-glycosidically linked side chain.

Since the hormone stimulates the formation of red blood cells, EPO is one of the Erythropoeiesis Stimulating Agents (ESA). ESA play an important role in blood formation (hematopoiesis). Erythropoietin can also be produced synthetically. The biotechnologically produced hormone is used to treat dialysis patients. With these, blood formation is often disturbed after kidney failure. Through various doping cases in sport, especially in cycling, erythropoietin became well known among the population.

Function, effect & tasks

Erythropoietin is made in the kidneys and released into the blood. It reaches the bone marrow via the blood, 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 takes place in seven steps.

First, so-called proerythroblasts arise from the multipotent myeloid stem cells in the bone marrow. Macroblasts arise from the proerythroblasts through division. The macroblasts in turn divide into basophilic erythroblasts. These are also known as normoblasts. The basophilic erythroblasts have 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.

The bone marrow then develops further into orthochromatic erythroblasts. The reticulocytes are formed by the 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 nucleated and organelle-free red blood cells take place.

However, the function of EPO is not limited to stimulating hematopoiesis. Studies have shown that the hormone can also be found in heart muscle cells and in various cells of the nervous system. Here it seems to influence cell division processes, the formation of new blood vessels (angiogenesis), the inhibition of apoptosis and the activation of intracellular calcium.

EPO could also be detected in the hippocampus. The hippocampus is a region of the brain that can be severely damaged in a short time by a lack of oxygen. In animal experiments it has been shown that the targeted administration of EPO increases the activity of the nerves in the hippocampus. In addition, a protective effect of the hormone in cerebral infarction and oxygen deficiency in the brain could be demonstrated.

Education, occurrence, properties & optimal values

85 to 90 percent of erythropoietin is produced by the kidneys. 10 to 15 percent of the hormone is made by the hepatocytes in the liver. Little synthesis also takes place in the brain, testes, spleen, uterus and hair follicles.

The biosynthesis of EPO is set in motion when the oxygen content in the blood is reduced. The transcription factors required for this are located on chromosome 7 in humans at position 7q21-7q22. In the event of a lack of oxygen, a subunit of the so-called hypoxia-induced factor (HIF) moves from the cell fluid to the nucleus of EPO-producing cells. There HIF binds to a suitable subunit. This creates the heterodimer HIF-1. This in turn binds to the cAMP response element binding protein and a special transcription factor. The end result is a protein complex that consists of three elements.

This binds to one end of the erythropoietic and initiates the 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 people, 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 & Disorders

A loss of function of the kidney can lead to an erythropoietin deficiency. As a result, too few red blood cells are produced and renal anemia occurs. Almost all patients with chronic kidney disease who have a serum creatinine value greater than 4 mg / dL develop such renal anemia.

Chronic kidney failure is mostly caused by diseases such as diabetes mellitus, hypertension, glomerulopathies, kidney inflammation (due to analgesic abuse), cystic kidneys and autoimmune diseases such as vasculitis.

The extent of renal anemia usually depends on the severity of the underlying disease. Those affected have a reduced performance and suffer from concentration disorders and susceptibility to infections. In addition, there are general symptoms such as tiredness, dizziness or pale skin. High blood pressure, gastrointestinal complaints, itching, menstrual disorders or impotence can also occur as part of anemia. Overall, the quality of life of the affected patients is significantly reduced. However, the formation of EPO is also inhibited by inflammation mediators such as interleukin-1 and TNF-alpha.

This is how anemia often develops in chronic diseases. Anemia occurs when inflammatory reactions persist for a long time. Chronic disease anemia is normocytic and hypochromic. This means that the red blood cells are normal in size, but do not carry enough iron.The symptoms of this form of anemia are similar to symptoms of iron deficiency anemia. The patients suffer from paleness, tiredness, concentration disorders, susceptibility to infections and shortness of breath.