LOCALIZATION OF SPECIFIC ERYTHROPOIETIN BINDING-SITES IN DEFINED AREAS OF THE MOUSE-BRAIN

The main physiological regulator of erythropoiesis is the hematopoieti c growth factor erythropoietin (EPO), which is primarily produced in t he kidney of adult mammals and is induced in response to hypoxia, Bind ing of EPO to the EPO receptor (EPO-R), a member of the cytokine recep tor superfamily, controls the terminal maturation of red blood cells, So far, EPO has been reported to act mainly on erythroid precursor tel ls. However, we have detected mRNA encoding both EPO and EPO-R in mous e brain by reverse transcription-PCR. Exposure to 0.1% carbon monoxide , a procedure that causes functional anemia, resulted in a 20-fold inc rease of EPO mRNA in mouse brain as quantified by competitive reverse transcription-PCR, whereas the EPO-R mRNA level was not influenced by hypoxia, Binding studies on mouse brain sections revealed defined bind ing sites for radioiodinated EPO in distinct brain areas, The specific ity of EPO binding was assessed by homologous competition with an exce ss of unlabeled EPO and by using two monoclonal antibodies against hum an EPO, one inhibitory and the other noninhibitory for binding of EPO to EPO-R, Major EPO binding sites were observed in the hippocampus, ca psula interna, cortex, and midbrain areas, Functional expression of th e EPO-R and hypoxic upregulation of EPO suggest a role of EPO in the b rain.