ABSTRACT
The metabolic fate of erythropoietin (EPO) remains unknown. Urinary excretion does not appear to play a major role and liver catabolism has been shown to occur only after terminal sugars on the hormone have been removed. However, it has been proposed that EPO is eliminated by consumption in the bone marrow. In order to examine the extent of such consumption we measured the half-life of radioidinated recombinant EPO injected intravenously (IV) to rats with bone marrows suppressed by cyclophosphamide or hypertransfusion and marrows stimulated by phenylhydrazine or bleeding. The mean half-life or erythropoietin in normal rats was 179 +/- 16 min, with similar half-lives found in the other rats regardless of decreased or increased bone marrow activity. The results indicate that it is unlikely that erythroid activity determines EPO life span and catabolism.
Subject(s)
Bone Marrow/metabolism , Erythropoietin/metabolism , Animals , Bone Marrow/abnormalities , Bone Marrow/pathology , Cyclophosphamide/pharmacology , Erythropoietin/administration & dosage , Half-Life , Hemorrhage/pathology , Hyperplasia/metabolism , Hyperplasia/pathology , Injections, Intravenous , Male , Phenylhydrazines/pharmacology , Rats , Rats, Inbred Strains , Recombinant Proteins/administration & dosage , Recombinant Proteins/metabolismABSTRACT
Serial erythropoietin measurements by RIA were performed in six patients with acute leukemia treated by intensive chemotherapy. In all cases erythropoietin titers increased after the onset of treatment, although the hemoglobin concentration remained at stable values. Subsequently the erythropoietin titers gradually returned to baseline levels. In same patients this reduction occurred at the end of chemotherapy, in others coincident with infections and antibiotic therapy. In four patients this decrease occurred at the time of bone marrow recovery. The explanation for this inappropriate increase in erythropoietin titers is not clear but may be related to a direct or indirect effect of a suppressed marrow on sites of erythropoietin production or catabolism.