Regulation of Erythropoiesis. Xv. Neonatal Erythropoiesis and the Effect of Nephrectomy.

The importance of erythropoietin as a regulator of erythropoiesis is undeniable, but that it is the sole regulator is controversial. Fried, Plzak, Jacobson, and Goldwasser (1) proposed a simple, unified concept for the regulation of red cell production. They suggested that the relationship of oxygen supply to demand governs the production of erythropoietin, which, in turn, through differentiation of the stem cells controls red cell production. An increased cell mass, e.g., through transfusion, in the presence of a normal Po2 would decrease erythropoietin production and erythropoiesis by increasing the oxygen supply. Conversely, anemia by decreasing the 02 supply would stimulate erythropoietin production. Changes in metabolic rate, e.g., starvation, would affect erythropoietin production and, hence, erythropoiesis by changes in 0° demand. As attractive as this hypothesis is, it does not appear to offer a satisfactory explanation for compensated hemolytic states (2), continued production of substantial numbers of red cells, although fewer than normal, in the polycythemic dog (3), or the stimulating effect of hemoglobin recently reported by Brown, Altschuler, and Cooper (4) and Sanchez-Medal, Labardini, and Loria (5). Jacobson, Goldwasser, Fried, and Plzak proposed the kidney as the site of production of erythropoietin (6). This conclusion was based on the striking decrease in erythropoiesis observed after bilateral nephrectomy but not ureteral ligation in the rodent. Similiar findings were reported by Naets in the dog (7), but Nathan, Schupak, Stohlman, and Merrill (8) observed substantially less suppression of red cell production in anephric