THE EFFECT OF STEROID METABOLITES ON THE HEMATOPOJETIC STEM CELL POOL

¹ Hematology Research Laboratory, Presbyterian-University of Pennsylvania Medical Center and Department of Hematology, The Medical College of Pennsylvania, Philadelphia, Pennsylvania
² Hematology Research Laboratory, Presbyterian-University of Pennsylvania Medical Center; Department of Hematology, The Medical College of Pennsylvania, Philadelphia, Pennsylvania

This study reports suggestive evidence for the ability of 3-hydroxy-5-pregnane-20-one, a steroid metabolite of testosterone, to trigger stem cells to a cell cycle stage responsive to the erythnoid differentiating effects of erythropoietin (ESF). Erythropoiesis was suppressed by the hypenoxic method of ESF suppression, to create an animal sensitive to exogenous enythropoietic stimuli. Mice maintained in hyperoxia were injected daily with the metabolite while controls received diluent injections. A significant elevation in erythropoiesis, as measured by ⁵⁹Fe incorporation into peripheral red blood cells, was observed in the metabolite-treated group 24, 48 and 72 hours after the initial injection. In another expeniment, mice receiving a single injection of the metabolite during hyperoxia were returned to ambient conditions 18 hours later. The observed erythropoietic response to the subsequent release of endogenous ESF, due to the temporary relative hypoxia of ambient conditions, was significantly higher in the metabolite-treated group than in the diluent-treated controls. The increment in erythropoietic response to the metabolite-, compared to the diluent-treated group, was greater in the posthyperoxic system, when rising titers of ESF are found, than in the hypenoxic system, suggesting that ESF may play a pimysioiogical role in the regulation of metabolite-induced erythropioesis.