Impaired Response of Polycythemic Mice to Erythropoietin Induced by Protein Starvation Imposed After Hormone Administration

Abstract

The present study was performed to determine the stage of the erythropoietic pathway which is affected by starvation or protein deprivation and whose manifestation is a depressed response to exogenous erythropoietin (EPO). The response to recombinant human EPO was measured in post-hypoxic polycythemic mice by determination of 59Fe uptake into red cells, spleen and femur and/or erythroid colony forming units (CFU-E) and erythroid precursor cell concentrations in femoral marrow. Experimental mice were either starved or fed one of seven different diets whose protein (casein) content ranged from 0 to 20%. All diets were isocaloric. The response of mice maintained on the standard diet (Purina Lab chow) was taken as the normal one. Starvation during the 48-hour period immediately before EPO injection had no effect on the response to the hormone. Starvation, and protein deprivation to a lesser extent, during the 48-hour period following EPO, on the other hand, significantly reduced the response. There was a progressive increase in the response as the casein content of the diet was increased. A normal response was observed when dietary casein concentration was 10%. These findings indicate that nutritional deprivation or dietary protein alterations during the period immediately following EPO injection in polycythemic mice can have detrimental effects on the erythroid response in a model in which nutritional deprivation was relatively short and acute. They also indicate that the subnormal response is not due to a decreased size of the erythroid progenitor pool available for differentiation but to deficient rates of differentiation of erythropoietic units.