Hemoglobin Synthesis in Short-term Cultures of Human Fetal Hematopoietic Tissues

Hemoglobin synthesis in the erythropoietic tissues of 11 normal human fetuses ranging in age from 6 to 21 wk has been studied. The incorporation of ³H-labeled and ¹⁴C-labeled leucine, valine, and isoleucine into the separated hemoglobins has been measured, and rates of synthesis of hemoglobins F₀, F₁, and A determined. Hemoglobin A synthesis could be detected in all of the embryos studied and was produced in fetal liver and spleen, as well as bone marrow and peripheral reticulocytes. The effect of a partially purified preparation of human erythropoietin (ESF: NIH, NHI Erythropoietin Committee; pool Al Ta LSL) on short-term cultures of these tissues has also been studied. Three phases of hepatic erythropoietin sensitivity have been observed. Early in gestation (before 10-12 wk), when the liver is predominantly an erythropoietic organ, cultured cells respond poorly to ESF; later (14-18 wk) as the hepatic functions of the liver begin to become dominant, maximal ESF sensitivity is achieved. At this time treated cultures synthesize up to ten times more hemoglobin than do controls. ESF responsiveness subsequently begins to decline, and by 21 wk only modest (1.5- to twofold) increments in hemoglobin synthesis are produced by ESF. No changes in the pattern of hemoglobins synthesized were noted as a consequence of ESF stimulation.