IMPORT OF THE GLUCOCORTICOID RECEPTOR INTO RAT-LIVER MITOCHONDRIA IN-VIVO AND IN-VITRO

Administration of inducing doses of dexamethasone (10 mug/100 g) to ad renalectomized rats results, within 2-5 min, in import of the glucocor ticoid receptor from liver cytoplasm into mitochondria, as demonstrate d by Western blotting and by electron microscopy. Furthermore, glucoco rticoid receptor (GR) synthesized in an in vitro reticulocyte system p rogrammed with the respective mRNA, enters within minutes to added rat liver mitochondria in the form of intact GR, as demonstrated by Weste rn blotting using either monoclonal or polyclonal antibodies against d ifferent domains of GR. In vitro studies show that the import is depen dent on temperature and/or activation of the hormone-GR complex. These results, in connection with the presence in the human and rodent mito chondrial genome of sequences showing partial homology to the nuclear glucocorticoid response elements, support the hypothesis that the well documented effects of glucocorticoids on mitochondrial functions resu lt from a direct interaction of the GR complex with the mitochondrial genome.