Evidence that renin substrate (angiotensinogen) may be a precursor of erythropoietin

We suggested a role for renin substrate (RS, angiotensinogen) in the biogenesis of erythropoietin (EP) (Nature 308:649-652, 1984). Purified RS was prepared from pooled plasma of healthy adult subjects, or from plasma of pregnant, healthy females. Antisera against human RS were shown to cross-react with purified human urinary EP, using a haemagglutination technique. On the other hand, antisera generated against highly purified human urinary EP showed strong cross-reaction with purified human plasma RS, by agglutinating erythrocytes covered with glutaraldehyde-coupled human RS. Moreover, using antisera generated against RS or EP, we have demonstrated monocytoid cells staining positive for both EP and RS in cerebellar haemangioblastoma tumors from 8 patients. Taken together, these observations point to a close relation between RS and EP. One interesting explanation is that renin substrate may be a precursor of erythropoietin.