Effect of erythropoietin on the peroxidase and tyrosine-iodinase activity of mouse thyroid and submaxillary gland

During an attempt to explore the mechanism of cobalt and vitamin B12 effect on the peroxidase and tyrosine iodinase activity, it was observed that cobalt and not vitamin B12in vivo elicits a high plasma titer of a humoral factor, erythropoietin, which caused increased 59Fe incorporation into red blood corpuscles. This erythropoietin was extracted from plasma or kidney and partially purified. This partially purified erythropoietin preparation when injected into starved rat caused increased 59Fe incorporation into red blood corpuscles. The potency of the partially purified erythropoietin preparation from plasma and kidney was compared. This partially purified erythropoietin, as well as sheep step-I erythropoietin, when administered to mice gave rise to a response almost similar to cobalt administration. It appears that the effect of cobalt on the peroxidase or tyrosine iodinase activity might be mediated through the elevation of the erythropoietin titer of plasma. Moreover, this erythropoietin was found to stimulate both peroxidase and tyrosine iodinase activity of the enzyme preparation of submaxillary gland in experiments in vitro. Erythropoietin, purified further in our laboratory, also produced the same effect. Neuraminidase-treated erythropoietin, in contrast, failed to execute any such stimulatory effect on the iodination of tyrosine

Studies on the in vitro formation of erythropoietin in sheep kidney medulla and the effect of cobalt thereon

Tissue slices of sheep kidney medulla catalyzed the incorporation of 14C-phenylalanine into protein when they were incubated in presence of twenty naturally occurring amino acids. Cobalt salt stimulated the incorporation significantly. Although slices from cortical or juxtaglomerular region of kidney catalyzed the incorporation of radioamino acid into proteins, yet no such stimulation of incorporation by cobalt salt was observed in those cases. The radioamino acid incorporated protein, produced under the influence of kidney medullary tissues in presence or absence of cobalt salt, was identified to be erythropoietin by its thermal stability, electrophoretic mobility on polyacrylamide gel and finally precipitation reaction with antierythropoietin