Is renin substrate an erythropoietin precursor?

The biogenesis of erythropoietin is incompletely understood. One hypothesis maintains that erythropoietin is synthesized primarily in the kidney while according to another theory an erythropoietin precursor present in plasma is activated by a renal factor, erythrogenin. An attractive candidate for the erythropoietin precursor is renin substrate (angiotensinogen) which has chemical similarities with erythropoietin. We show here that purified renin substrate from human plasma is immunologically related to human erythropoietin. Moreover, purified renin substrate, like erythropoietin, causes the dose-dependent increase of haemoglobin F in cultured human erythroid leukaemia K562 cells. We conclude that renin substrate is a likely precursor of erythropoietin.