IMPAIRED RESPONSE OF POLYCYTHEMIC MICE TO ERYTHROPOIETIN-INDUCED BY PROTEIN STARVATION IMPOSED AFTER HORMONE ADMINISTRATION

The present study was performed to determine the stage of the erythrop oietic pathway which is affected by starvation or protein deprivation and whose manifestation is a depressed response to exogenous erythropo ietin (EPO). The response to recombinant human EPO was measured in pos t-hypoxic polycythemic mice by determination of Fe-59 uptake into red cells, spleen and femur and/or erythroid colony forming units (CFU-E) and erythroid precursor cell concentrations in femoral marrow. Experim ental mice were either starved or fed one of seven different diets who se protein (casein) content ranged from 0 to 20%. All diets were isoca loric. The response of mice maintained on the standard diet (Purina La b chow) was taken as the normal one. Starvation during the 48-hour per iod immediately before EPO injection had no effect on the response to the hormone. Starvation, and protein deprivation to a lesser extent, d uring the 48-hour period following EPO, on the other hand, significant ly reduced the response. There was a progressive increase in the respo nse as the casein content of the diet was increased. A normal response was observed when dietary casein concentration was 10%. These finding s 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 mode l in which nutritional deprivation was relatively short and acute. The y also indicate that the subnormal response is not due to a decreased size of the erythroid progenitor pool available for differentiation bu t to deficient rates of differentiation of erythropoietic units.