Regulation of red blood cell production.

Erythropoietin, which is produced by peritubular capillary lining cells of the kidney, is critical to the production of red blood cells. Endogenously produced erythropoietin circulates in the plasma to act on specific target cells in the marrow through cell surface receptors. The primary target of erythropoietin action is the erythroid colony-forming cell. In addition to proliferative effects, high circulating erythropoietin levels result in the premature release of marrow reticulocytes and the mobilization of marrow progenitor cells. Production of endogenous erythropoietin increases in response to the stress of anemia or hypoxemia. Iron, an important element in hemoglobin synthesis, is bound to the iron transport protein transferrin, and the complex is internalized, along with the transferrin receptor, by the developing erythroid cell. Within the cell, the iron molecule is subsequently split off and either used for hemoglobin synthesis or stored within the cytoplasm as ferritin. Administration of recombinant human erythropoietin induces changes in iron metabolism, which are reflected by decreases in both the serum iron level and transferrin saturation. These reductions can be marked, even in healthy individuals, and can occur in the presence of normal or even increased iron stores.