Effects of increasing time between nephrectomy and hypoxia on extrarenal erythrogenin
Hamburger, S.A.; Kaplan, S.M.; Derelanko, M.J.; Meagher, R.C.; Roy, M.; Harvey, K.M.; Camiscoli, J.F.; Gordon, A.S.
American Journal of Physiology 234(6): F510-F513
1978
ISSN/ISBN: 0002-9513 PMID: 580856 Document Number: 137297
The kidney is well established as the primary site of origin or activation of erythropoietin (Ep). However, the precise mechanism of Ep formation has not been unequivocally established. Evidence was presented to show that in response to hypoxia, the kidney elaborates a renal erythropoietic factor termed erythrogenin, which interacts with a serum substrate to produce Ep. Recently the liver and spleen were implicated as the major sites of extrarenal Ep production. Because Ep often cannot be detected in the serum of anephric rats despite exposure to intense hypoxia, experiments were designed to determine whether erythrogenin is produced by extrarenal sites at times after nephrectomy when serum Ep is low or undetectable. Young male rats were nephrectomized 6, 12, 18, or 24 h before exposure to 6 h of intense hypoxia (0.35 atm of Ep generated), decreased (.apprx. 0.05 U) at 12 h postoperatively, and rose to a high level (.gtoreq. 0.14 U) at 24 h after surgery. A low level of erythrogenin (.apprx. 0.04 U Ep generated) was observed in ureter-ligated control animals at all time intervals. Despite increased tissue erythrogenin in nephrectomized rats, only small amounts of serum Ep were detected (.ltoreq. 0.06 U). The results suggest that in the anephric animal, release of erythrogenin from extrarenal sites may be prevented, the activity of erythrogenin-mediated Ep production may be inhibited by undetermined mechanisms, or an additional unidentified factor required for normal Ep production is not present.