Regulation of EPO production

The level of EPO production in the kidneys (or liver) is primarily regulated by the oxygen demand of the producer cells, relative to their oxygen supply. Under normal conditions, when the producer cells are supplied with adequate oxygen via the blood, EPO (or EPO mRNA) levels are barely detectable. However, the onset of hypoxia (a deficiency of oxygen in the tissues) results in a very rapid increase of EPO mRNA in producer cells. This is followed within 2 h by an increase in serum EPO levels. This process is prevented by inhibitors of RNA and protein synthesis, indicating that EPO is not stored in producer cells, but synthesized de novo when required. 

Interestingly, hypoxia prompts increased renal and hepatic EPO synthesis in different ways. In the kidney, the quantity of EPO produced by an individual cell remains constant, while an increase in the number of EPO-producing cells is evident. In the liver, the quantity of EPO produced by individual cells appears to simply increase in response to the hypoxic stimulus. 

A range of conditions capable of inducing hypoxia stimulate enhanced production of EPO, thus stimulating erythropoiesis. These conditions include  

On the other hand, hyperoxic conditions (excess tissue oxygen levels) promote a decrease in EPO production. 

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