Erythropoietin: from bench to bedside

Erythropoietin is unique amongst the hematopoietic growth factors since it is the only one which behaves like a hormone. The development of sensitive immunoassays for erythropoietin have provided an opportunity to examine its physiology more closely than ever before. Although the classical inverse-linear correlation between erythropoietin and hemoglobin has been amply confirmed, it has also become apparent that this relationship is tightly regulated and is only apparent below a threshold hemoglobin and not fully operative within the normal range of hemoglobin values. Certain disease states blunt the response of erythropoietin-producing cells to anemia, and in some cases this appears to be due to a resetting of the threshold for response while in others there may be a dichotomy between activation of the machinery for erythropoietin gene expression and net protein synthesis. The tight regulation of erythropoietin production may be directed in part at preventing explosive increases in the red cell mass and in part may conform to the actual demands of erythroid progenitor cells for the hormone, since, at least in vitro, erythropoietin effects these progenitor cells differently according to their stage of maturation and sustained high levels of the hormone are not necessary for certain of the desired effects.