EPO Regulation

One of the most extensively studied systemic adaptations to hypoxia is the stimulation of red blood cell (RBC) production. Over 100 years ago, Paul Bert and Denis Jourdanet observed the association between reduced atmospheric oxygen pressure and elevated RBC numbers in the blood of animals and humans (1, 2, 3). Francois-Gilbert Viault then demonstrated that ascent to a high altitude provided an acute and direct physiological stimulus for RBC production during his 1890 expedition to the Peruvian Andes by measuring the RBC increases in his own and the blood of his companions (4). It was the interest in understanding the physiological and molecular basis of this erythropoietic response that led to the discovery of erythropoietin (EPO) and that paved the way for the identification of the molecular machinery that senses oxygen and controls a wide spectrum of tissue-specific and systemic responses to hypoxia, including EPO regulation.