Factors Stimulating Erythropoiesis In

By WENDELL F. RossE, THOMAS WALDMANN AND ELEANOR Huu. H YPOXIA AND ANEMIA have been known for many years to stimulate erythropoiesis in mammals, including man.1 In recent years, these stimuli have been shown to have their effect through a humoral factor, erythropoietin.2 J acobson, et al. have suggested that lack of oxygen, relative to the metabolic needs of the animal, is the fundamental stimulus for erythropoiesis and that this relative lack is sensed by some portion of the body, resulting in the production of erythropoietin.3 The lack of oxygen in the sensitive tissues may be due to hypoxic environment, to reduction of circulating hemoglobin, to the histotoxic effects of chemicals or, on the other hand, to an increase in tissue oxygen needs due to elevation of the rate of metabolism. There is some evidence that this hypothesis may not hold for lower animals. Chronic hypoxia does not induce polycythemia in turtles,4 frogs5’6 or lizards,6 although this response is said to occur in newts7 and fish.8 No reticulocytosis is seen in response to acute or chronic anoxia in the turtle although evidence of increased erythropoiesis is seen in response to bleeding.4 The present experiments were designed to test the erythropoietic response of frogs to bleeding, hypoxia, and to cobaltous ion administration. The response was measured by determining the incorporation of thymidine-2-C” into circulating erythrocytes. This compound is incorporated into desoxyribonucleic acid only of dividing cells; is not exchanged, once incorporated, until the cell dies; and is not incorporated into the non-dividing cell.#{176} This same system was used to test the erythropoietic effect of various sera.