DNA Synthesis is Essential for Increased Haemoglobin Synthesis in Response to Erythropoietin

Abstract

MAMMALIAN erythropoietic stem cells differentiate into granulocytes or erythrocytes. In differentiating into erythrocytes they go through several maturation divisions during which the basophilia of the cytoplasm diminishes, protein accumulates and the nucleus changes its structure and is eventually expelled. The most basophilic cells make little or no haemoglobin whereas most of the metabolism of reticulocytes is directed to its synthesis. Maturation of these cells is stimulated by erythropoietin, a glycoprotein produced in the kidney in response to low oxygen tension in the blood. This stimulation can be studied in cultured bone marrow or foetal liver cells. It has been shown that the response involves both haemoglobin and RNA synthesis; RNA synthesis occurs first and the entire process can be eliminated by treatment with actinomycin D¹. We report here experiments which show that DNA synthesis is a prerequisite for any increase in haemoglobin synthesis following erythropoietin, although cell division is not.