Responsiveness of Hematopoietic Tissue to Erythropoietin in Relation to the Time of Administration and Duration of Action of the Hormone

Following the injection of erythropoietin either in a single large dose or in multiple doses, a change in the responsiveness of the hematopoietic tissue occurs. The fact that different doses of erythropoietin stimulate erythropoiesis to the same extent when the action of the hormone is limited to 6 hours by the injection of antibody suggests that the stem cells are receptive to the action of erythropoietin only at some limited time in their individual life cycle. It is suggested that this period is sometime after metaphase and before the commencement of DNA synthesis in the interphase state of individual stem cells. It is further suggested that the increased responsiveness of the hematopoietic tissue to erythropoietin following injection is due to recruitment of stem cells into this receptive state. This recruitment may be due to both the division of stem cells and the movement of cells through cell cycle into the receptive state. The results are discussed in relation to two recent models of stem cell kinetics.