Stem Cells, Vol 11, 296-302, Copyright © 1993 by AlphaMed Press
Impaired response of polycythemic mice to erythropoietin induced by protein starvation imposed after hormone administration
AC Barcelo, RM Alippi, P Boyer, MI Olivera, SM Mide, J Caro and CE Bozzini
Department of Physiology, University of Buenos Aires, School of Dentistry, Argentina.
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.
