Erythropoietin: An Historical Overview of Physiology, Molecular Biology, and Gene Regulation

The scope of this chapter is to provide a historical overview of the physiology, molecular biology, and gene regulation of erythropoietin. Commencing with seminal observations of classical medicine linking the blood, oxygen, erythropoiesis, and the kidney, the field progressed into an era of experiments into the whole body physiology, demonstrating the presence of a circulating hormone, “erythropoietin,” which is produced by the kidneys, in response to tissue hypoxia, and stimulates erythropoiesis in the bone marrow. Part of the 20th-century analysis of the mechanism of erythropoietin gene regulation provided insight into major oxygen-regulated transcriptional pathways extending far beyond erythropoiesis. Processes as diverse as angiogenesis, vasomotor control, glycolysis, tricarboxylic acid cycle metabolism, inflammation, apoptosis, and cell cycle control are involved, and these highly conserved signaling pathways are integral to animal cell biology. These advances have provided possible therapeutic targets not just for the treatment of anemia but also for major disease processes, such as neoplasia and ischemia.