Response to Erythropoietin. ∗

Abstract

Alpen and Cranmore (1) and Erslev (2) have concluded that erythropoietin increases red cell output by accelerating the rate of stem cell differentiation into erythroid precursors. Observations on erythropoiesis in polycythemic mice by Gurney, et al.(3) have supported this conclusion. However, observations by several investigators (4-7) seem to indicate that the action of the erythropoietic humoral factor (s) is not limited to regulation of stem cell differentiation. Experiments reported here tested the effect of erythropoietin on later phases of erythroid formation and the results suggest an action here as well as in the early stem cell phase.

Methods. Female Sprague-Dawley rats, weighing 180 to 200 g, were made polycythemic by one or several transfusions of packed homologous red blood cells. Each transfusion equaled 50% of the animal's original red cell mass. At various intervals following the initial transfusion the polycythemic rats were given a single injection of human urine erythropoietin (8) or purified sheep erythropoietin (9).‡ Subsequent changes in erythropoiesis were assessed by reticulocyte counts (10) and measurement of the 18-hour erythrocyte radio-iron incorporation(8). Erythroid elements per 1000 nucleated cells were enumerated in smears of marrow from control polycythemic animals.

In 3 experiments, polycythemic rats were given single intraperitoneal injections of 2 ml of urine concentrate on either the 5th, 15th or 31st day after their first transfusion. Control polycythemic rats were injected with saline. At the end of each successive 24-hour period following erythropoietin or saline injection, representative animals from each group were killed and the reticulocyte counts, hematocrits and erythrocyte radio-iron incorporation were determined. The radio-iron was injected 18 hours before the rats were killed. All groups given urine concentrate included at least 5 rats.