Biologic and immunologic erythropoietin in extracts from hypoxic whole rat kidneys and in their glomerular and tubular fractions.

The relationship between plasma erythropoietin levels and kidney erythropoietin content was studied in rats subjected to hypoxia for various periods. Plasma and kidney erythropoietin followed a parallel course with detectable levels observed as early as after 1 hour of hypoxia. However, the kidney erythropoietin content reached a maximum at 6 hours, and its plasma erythropoietin content reached its maximum at 24 hours. Despite continuous hypoxia, the erythropoietin in both kidney and plasma decreased after reaching their maximal values, and leveled off after 72 hours. This parallel decrease in plasma and kidney erythropoietin suggests that this decrease in plasma erythropoietin observed after prolonged hypoxia is secondary to a decrease in erythropoietin production rather than to an increase in peripheral consumption. To identify the cell(s) involved in erythropoietin production, kidney cells from anemic-hypoxic animals were separated into their glomerular and tubular components utilizing a successive sieving procedure. Measurement of erythropoietin by bioassay revealed four to five times as much erythropoietin in the tubular fraction as in the glomerular fraction. Radioimmunoassay of these fractions revealed erythropoietin content similar to that by bioassay, ruling out the possible presence of biologically nonactive material. Renin activity, on the other hand, was about equally distributed between both of these fractions. Although our studies do not rule out participation of glomerular or juxtaglomerular cells in erythropoietin production, they suggest that a tubular origin of the bulk of renal erythropoietin is more likely.