Erythropoietin and the Regulation of Erythropoiesis

Abstract

The profusion of data which has sprouted in the last 20 years on red blood cell (RBC) regulation is so phenomenal as to be frightening. We have passed from the speculation of a circulating humoral factor controlling hemoglobin synthesis to a highly developed model supported by clinical, animal, and biochemical evidence. Erythropoietin, found in plasma and urine, is produced in response to tissue hypoxia and within minutes accelerates RNA synthesis in RBC precursors. This humoral response to oxygen deficit occurs predominantly in the kidney where an enzyme found in the light mitochondrial fraction, in the presence of normal plasma, forms erythropoietin. Thus, the anemia of renal disease results largely from failure of the kidneys to synthesize this hormone whereas most cases of aplastic anemia are the result of failure of the marrow to respond to high circulating levels of erythropoietin. Krantz and Jacobson have taken the deluge of information and