Mechanism underlying the inhibitory effect of dexamethasone on in vivo erythropoiesis

Abstract

The time-response curve for RBC-59Fe uptake following i.p. injection of 5 mg of dexamethasone into normal, non-polycythemic mice, shows a maximal depression (50% of normal) at 3 days after dexamethasone with return to almost normal values by 5 days. The effect is dose-related showing a plateau with doses of dexamethasone above 3 mg. The shape of the time-response curve indicates that the more mature cells in the erythron are not affected by dexamethasone and that the major effect of the steroid must be on earlier erythroid cells. Intravenous injection of dexamethasone 33 and 48 h after i.v. injection of erythropoietin in post-hypoxic polycythemic mice has no effect on the response to erythropoietin, suggesting that the early and late erythroblasts develop normally into erythrocytes. Injection of dexamethasone 13 h after erythropoietin is also ineffective, suggesting that the final steps of differentiation from erythropoietin responsive cells (ERC) to proerythroblasts are not affected. On the contrary, injection of dexamethasone 1 h after erythropoietin reduces by 60% the effective erythropoiesis, which can be attributed to a decrease in differentiation of ERC into proerythroblasts. These results indicate that the inhibitory action of dexamethasone on erythropoiesis is exerted on cells of the erythroid line before the stage of proerythroblast is reached.