As reported previously (Pflügers Arch 499, Suppl 1, S112, 2005), an elevation of the intracranial pressure leads to a significant increase in plasma Epo concentrations. In order to proof the involvement of a brainstem factor in renal epo synthesis, we investigated cerebral Epo production by real time RT PCR. Hypobaric hypoxia (increased ICP: 100mmHg for 10 min) and anaemic hypoxia (lowering of the hematocrit from 40 to 30%) led to a 2- to5fold induction of the Epo gene expression in all examined brain areas (cortex, brainstem, cerebellum and hypothalamus), with the exception of the hypophysis. Here, increasing of the ICP led to a 100fold induction of the Epo mRNA, whereas anaemic hypoxia led to a downregulation of the Epo gene expression. Hence, the hypophysis seems to differ from the rest of the brainstem. Microdialysates from the hypothalamus / hypophyseal area, collected under both eyperimental procedures, increased Epo production in HepG2 cells during normoxia. Homogenates from the hypophysis showed comparable spot development under both experimental conditions in 2D- gelelectrophoresis.

These findings support our hypothesis that the hypophysis plays a major role in the regulation of the renal epo production. Under hypoxic conditions the hypophysis releases one or more humoral factors, which trigger Epo synthesis in the kidney.