Role of erythropoietin in adaptation to hypoxia.
The glycoprotein hormone erythropoietin (EPO) counteracts tissue hypoxia by increasing the systemic oxygen-carrying capacity. It induces augmentation of red blood cell mass by stimulating the formation and differentiation of erythroid precursor cells in the bone marrow. EPO production is increased under various forms of diminished oxygen supply such as anemic or hypoxic hypoxia. In the adult organism, the kidneys are the major source of EPO. The precise nature of the cells responsible for renal EPO production, however, has not yet been elucidated. Most likely, peritubular cortical cells, e.g. interstitial or endothelial cells, are involved in the elaboration of the hormone. From the observation that isolated perfused rat kidneys produce EPO in an oxygen-dependent fashion we conclude that the 'oxygen sensor' that controls hypoxia-induced EPO synthesis is located in the kidney itself. Within the kidneys, the local venous oxygen tension which reflects the ratio of oxygen supply to oxygen consumption is measured and transformed into a signal that regulates the formation of EPO. However, the mechanism by which a decrease of oxygen delivery to the kidneys is linked to an enhanced EPO gene expression is not yet known. Two possible mechanisms of regulation are discussed: First, renal hypoxia could lead to enhanced formation of metabolic mediators, for example prostaglandins or adenosine, which might stimulate EPO gene transcription by increasing cellular levels of second messenger molecules. Second, some kind of molecular 'oxygen receptor' such as a heme protein, that controls EPO formation by an oxygen-dependent conformational change, could mediate signal transduction.
Scholz
H
H
Physiologisches Institut der Universität, Zürich, Switzerland.
Schurek
H J
HJ
Eckardt
K U
KU
Bauer
C
C
D000818:Animals; D004921:Erythropoietin / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007668:Kidney / Q000502:physiology; D015398:Signal Transduction
D004921:Erythropoietin