Studies on an Inhibitor of Erythropoiesis. II. Inhibitory Effects of Serum from Uremic Rabbits on Heme Synthesis in Rabbit Bone Marrow Cultures

Abstract

Summary The effects of sera from anephric rabbits on the rate of heme synthesis in erythroid cells were studied in vitro in rabbit bone marrow cultures. Sera from nephrec-tomized rabbits significantly (P < 0.05) inhibited ⁵⁹Fe incorporation into heme in normal rabbit bone marrow cultures incubated with erythropoietin (ESF) when compared with the response in control cultures with normal serum and ESF. This inhibitory activity increased exponentially with increasing concentrations of the serum in cultures suggesting that a higher concentration of the inhibitor is present in uremia and may be the result of the failure to excrete the inhibitor. This suggests that the retention of this inhibitor may play an important role in the mechanism of the anemia of uremia. The inhibitor of heme synthesis is a low molecular weight substance.