Erythropoietin requirement for the maintenance of normal levels of erythropoiesis in the normal adult mouse.

Abstract

Erythropoietin (EPO) is a glycoprotein which appears as the primary regulator of erythropoiesis under either normal or most of the pathologic conditions. In the rat with experimentally-reduced erythropoiesis, daily administration of 1.3 IRP units can restore the function and maintain steady-state conditions of red cell formation. This important information for the programming of both physiologic and pharmacologic studies is lacking for the mouse, in spite of the fact that most of the experiments performed on the regulation of erythropoiesis have been conducted in this species. In the present study, designed to determine EPO requirement for maintenance of steady-state erythropoiesis in the adult mouse under standard laboratory conditions, adult females of the CF#1 strain were exposed to hypobaria (18 h/day) during a 3-week period for induction of polycythemia (P). At the end of the hypoxic period. P mice were maintained at sea level conditions, as were normocythemic (N) mice during the entire experimental period. P mice were daily injected with 0, 0.5, 1.0, 1.5, or 2.0 IRP units of rHu-EPO during the 4-day period that followed the hypoxic one. The rate of erythropoiesis in N and P mice were measured by RBC-59Fe uptake. The plasma 59Fe half-clearance time was also measured in other groups of N and P mice similarly treated. One-way ANOVA showed that the only non-significant difference (P > 0.05) between N and EPO-injected P mice was established for the 1.0 unit dose group. It is thus suggested that approximately 1.0 unit of EPO should be synthesized daily in an adult mice to maintain a normal rate of erythropoiesis.