Erythropoietin in the control of red cell production.
The understanding of the endocrine regulation of red cell production has been extended greatly since the erythropoietin gene was cloned and recombinant human erythropoietin has become available for experimental and clinical applications. Human erythropoietin is a 30 kDa glycoprotein. It is composed of 165 amino acids and 4 carbohydrate side chains. Studies in rodents have shown that blood-borne erythropoietin originates from peritubular cells, possibly fibroblasts, in the renal cortex and from parenchymal cells in the liver. In addition, erythropoietin mRNA has been demonstrated in spleen, lung and brain. Tissue hypoxia is the main stimulus for erythropoietin synthesis. Erythropoietin gene expression is controlled by DNA-binding proteins, primarily by hypoxia-inducible factor 1. Erythropoietin maintains red cell production by inhibiting apoptosis of erythrocytic progenitors, and by stimulating their proliferation and differentiation into normoblasts. The functional human erythropoietin receptor, a 484-amino acid glycoprotein, is member of the class I cytokine receptor superfamily. Lack of erythropoietin results in anaemia. Recombinant human erythropoietin is efficient for treatment of the anaemia of chronic renal failure. In addition, the drug is increasingly administrated to persons suffering from anaemia of chronic diseases and to surgical patients, thus abolishing the need for homologous red cell transfusion.
Jelkmann
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Institut für Physiologie, Medizinische Universität zu Lübeck.
Metzen
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D000818:Animals; D004920:Erythropoiesis; D004921:Erythropoietin / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000502:physiology; D051379:Mice; D010100:Oxygen / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000502:physiology
D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D010100:Oxygen