Hypoxia and Erythropoietin Production

  • James W. Fisher
  • M. Ueno
  • J. Nakashima
  • Barbara Beckman
Part of the Clinical Physiology Series book series (CLINPHY)


Hypoxia is known to be the fundamental stimulus for the control of erythropoietin production (13, 14, 20, 31). Several external messenger substances are released during hypoxia, which activate adenylate cyclase, and increase the generation of the second messenger cyclic AMP, which is involved in the regulation of erythropoietin (Ep) production (14, 20). Some of the factors that are known to be released during hypoxia and seem to be involved in the regulation of Ep production are adenosine (37), oxygen-derived metabolites (38), eicosanoids (26), and beta2-adrenergic agonists (12). These external messenger substances can act alone or in concert to trigger receptors that activate stimulatory G proteins in the membrane of a renal Ep-producing cell, and increase adenylate cyclase and cyclic AMP. Cyclic AMP causes the dissociation of the regulatory subunit from the catalytic head of protein kinase A. Important phosphoproteins are generated by kinase A in the kidney, which may lead to increased biosynthesis of Ep at the level of transcription of messenger RNA or the translation of Ep in the renal cell. In addition, phosphoproteins could be involved with the actual release process for Ep in the cell. Atrial natriuretic factor (ANF) is known to be released during hypoxia (2, 3) and to increase Ep secretion in renal carcinoma cells in culture through an ANF receptor mechanism coupled to guanylate cyclase (39). The purpose of this presentation is to review the regulatory factors that may be involved in hypoxic stimulation of kidney production of Ep.


Xanthine Oxidase Renal Carcinoma Atrial Natriuretic Factor Ischemic Hypoxia Reactive Oxygen Metabolite 
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© American Physiological Society 1991

Authors and Affiliations

  • James W. Fisher
  • M. Ueno
  • J. Nakashima
  • Barbara Beckman

There are no affiliations available

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