title: 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.
authors.affiliation: Department of Physiology, University of Buenos Aires, School of Dentistry, Argentina.
authors.forename: A C
authors.initials: AC
authors.lastname: Barceló
authors.forename: R M
authors.initials: RM
authors.lastname: Alippi
authors.forename: P
authors.initials: P
authors.lastname: Boyer
authors.forename: M I
authors.initials: MI
authors.lastname: Olivera
authors.forename: S M
authors.initials: SM
authors.lastname: Mide
authors.forename: J
authors.initials: J
authors.lastname: Caro
authors.forename: C E
authors.initials: CE
authors.lastname: Bozzini
mesh_terms: D000818:Animals; D002364:Caseins / Q000008:administration & dosage / Q000494:pharmacology; D004044:Dietary Proteins / Q000008:administration & dosage / Q000494:pharmacology; D004351:Drug Resistance; D004906:Erythrocyte Count; D015672:Erythroid Precursor Cells / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D007501:Iron / Q000493:pharmacokinetics; D051379:Mice; D011086:Polycythemia / Q000503:physiopathology*; D011488:Protein Deficiency / Q000503:physiopathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012156:Reticulocytes; D013217:Starvation / Q000503:physiopathology
chemical_list: D002364:Caseins; D004044:Dietary Proteins; D011994:Recombinant Proteins; D004921:Erythropoietin; D007501:Iron