Production of and response to erythropoietin in the splenectomized mouse

A reliable dose-response curve has been established by exposing normal mice to graded doses of exogenous erythropoietin (ESF). In CF1 femal mice, made polycythemic by exposure to reduced air pressure , 59 Fe incorporation in RBC following injections of ESF (ranging from 0.05 to 3.2 IRP-units) varied according to the log of the ESF dose from 2.5 to 29.0 percent. Experiments with plethorized splenectomized mice showed unequivocally that they were able to respond to ESF, although their responses were very much smaller than that of intact mice, ranging from 1.4 to 12.0 percent. ESF activity was not detected in plasma from intact mice, but was evident in the plasma of mice that had been splenectomized 4 or 10 days earlier. Under conditions of hypoxia the plasma ESF level rose rapidly during the first 48 hours and then fell . In the plasma of splenectomized, similarly treated mice, the ESF level at every interval studied was much higher and was maintained for a longer time. Re-exposure to low oxygen tension for brief periods (2-24 h) produced and erythropoietic response in both intact and splenectomized polycythemic mice, its magnitude increasing with increased exposure time. The response of splenectomized mice, however, was lower than that of intact mice in spite of the fact that the plasma ESF level in the former was higher than in the latter.