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the erythrogenin theory states that the kidney, in response to hypoxia , produces a substance that enzymatically converts a circulating a-globulin to active Ep.The renal erythropoietic factor is called erythrogenin and the plasma substrate , which is thought to be of hepatic origin ,is called erythropoietinogen.such a factor has been extracted from the light mitochondrial fraction of kidneys and is capable of generating Ep when incubated with palsma from normal animals . this factor has litte direct effect on erythropoiesis in plethoric mice , this work has been reproduced in some laboratories , but not in others. According to the proerythropoietin theory , the kidneys produce an inactive molecule which contains intact Ep.Evidence for this consists of the following :Incubation of a light mitochondrial fraction from hypoxic rat kidneys with serum from normal rabbits results in active Ep which is immunologically rat in origin .Antibody to Ep labeled with fluorescein binds to renal glomeruli, which indicates the presence of Ep in the kidneys. The inhibitor theory suggests that complete Ep is produced by the kidney, but it may be inactivated by a lipid-soluble inhibitor during the extraction process. Contact with normal serum neutralizes the inhibitor and allows extraction of biologically active Ep.Further support for this ,and also the pro-Ep theory, comes from the observation that when hourly Ep production in an intact hypoxic medium almost completely free of serum, production of Ep continued , which indicates that the kidneys were capable of producing the hormone without need for much serum protein. A consensus does not yet exist on how Ep is made by the kidney .Much more work is necessary to determine which of the above hypotheses might be correct. however, it seems clear that the kidney is the principal site regulating production of the hormone .

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