Biogenesis of erythropoietin: role of the substrate for erythrogenin.

Abstract

Abstract Intravenous administration of erythrogenin (REF) to normal rats resulted in the appearance of significant quantities of erythropoietin (ESF) in the plasma of these animals. The plasma ESF activity, first evident at 2 hours after REF injection, was preceded by a significant rise in the concentration of the substrate for REF. Similar results were obtained when hypoxia was used to stimulate the release of endogenous REF. Fluctuations in the levels of the circulating ESF and the substrate for REF suggest that the negative feedback action of the ESF on its own production is mediated through a decrease in the amount or availability of the substrate. Exposure of rats to only 1 hour of hypoxia was sufficient to evoke the reactions leading to the formation of the ESF. These events proceeded independently of the hypoxic stimulus for at least 5 hours after its interruption and resulted in the production of significant quantities of ESF.