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 adrenalectomized rats results, within 2-5 min, in import of the glucocorticoid receptor from liver cytoplasm into mitochondria, as demonstrated by Western blotting and by electron microscopy. Furthermore, glucocorticoid receptor (GR) synthesized in an in vitro reticulocyte system programmed with the respective mRNA, enters within minutes to added rat liver mitochondria in the form of intact GR, as demonstrated by Western blotting using either monoclonal or polyclonal antibodies against different domains of GR. In vitro studies show that the import is dependent on temperature and/or activation of the hormone-GR complex. These results, in connection with the presence in the human and rodent mitochondrial 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 result from a direct interaction of the GR complex with the mitochondrial genome.