Interstitial cells lining the peritubular capillaries of human adult kidneys produce erythropoietin.
EPO-R is activated upon dimerization following EPO interaction. After binding, EPO is rapidly internalized and undergoes endocytosis and degradation. There are no preformed stores of erythropoietin. It is regulated at the gene level and production is independent of plasma concentration. Since the only physiologic stimulus for its production is tissue hypoxia, plasma erythropoietin concentration can be used as a measure of tissue oxygenation.