Erythropoietic kinetics in sheep studied by means of induced changes in hemoglobin phenotype

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Abstract
This investigation is concerned with the kinetics of the reciprocal relationship between sheep hemoglobin (Hb) A and Hb C formation in response to anemia. The relative synthesis of the hemoglobin types was assessed at various times in bone marrow erythroid cells incubated in vitro with 59Fe. The changeover from Hb A to Hb C formation lagged by about 3 days behind the development of anemia and was complete within about 11 days. After recovery from anemia the reciprocal change back to preanemic conditions proceeded at a much slower rate, Hb C formation gradually declining to unmeasurable levels over about 25 days. Infusions of plasma with high erythropoietin titre induced the formation of relatively large quantities of Hb C in erythroid cells of nonanemic sheep, demonstrating the central importance of a humoral mechanism in the change of expression of the hemoglobin genes. The following conclusions were drawn: hemoglobin phenotype is determined at a stem cell level. Erythroid stem cells appear to undergo gradual renewal. The identity of the plasma factor which induces Hb C formation is not yet known; it is not present in plasma from nonanemic sheep, and its production is not dependent upon hemoglobin genotype. If the plasma factor turns out to be erythropoietin, then this hormone must have an important influence on the pool of erythroid stem cells.