Insulin potentiates the transactivation potency of the glucocorticoid receptor.

A single copy of a glucocorticoid-responsive element (GRE) is sufficient in mediating the combinatorial response of a promoter to both glucocorticoids and insulin in HepG2 cells. This requires the presence of active glucocorticoid receptor (GR) since the response is significantly inhibited by the anti-glucocorticoid RU30406. The N'- and C'-terminal parts of the GR protein are not involved in mediating the response.

The mitochondrion as a primary site of action of glucocorticoids: the interaction of the glucocorticoid receptor with mitochondrial DNA sequences showing partial similarity to the nuclear glucocorticoid responsive elements.

Six mitochondrial genome sequences, showing strong similarity to the glucocorticoid responsive element consensus sequence (GRE), four localized within the cytochrome c oxidase (COX) subunit I and II genes (GREs I-IV) and two within the D-loop region (GREs a and b) have been examined as binding sites of glucocorticoid receptor (GR) from rat liver cytosol. Purified GR from rat liver cytosol binds with high specificity to all potential mitochondrial GREs, as shown by filter retention and gel shift assays. Specific binding of protein(s), present in a mitochondrial extract from dexamethasone-induced mice, to all six putative mitochondrial GREs was also documented by the same methodology.

The c-fos serum response element (SRE) confers negative response to glucocorticoids.

Ligand activated Glucocorticoid Receptor (GR), specifically inhibited the serum induced c-fos promoter activation in NIH3T3 fibroblasts. The negative control was mediated by the c-fos SRE and correlated with the relative abundance of active GR. Serum activated SRE was repressed 3-4-fold by glucocorticoids irrespective of the promoter context (heterologous or authentic).

Import of the glucocorticoid receptor into rat liver mitochondria in vivo and in vitro.

Administration of inducing doses of dexamethasone (10 microg/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.

Interaction of cytosol fractions containing activated glucocorticoid-receptor complexes from rat liver and thymus with heterologous nuclei: effects on transcription.

Two rat liver cytosol fractions containing activated glucocorticoid-receptor complexes are able to stimulate the transcriptional activity of rat liver nuclei; the respective fractions from the cytosol of thymocytes inhibit the capacity of thymus nuclei for RNA synthesis. A similar inhibitory effect on thymus nuclei is exerted by the presence of rat liver cytosol fractions. Spot hybridization using a tyrosine aminotransferase (TAT) probe demonstrates that TAT gene expression is stimulated by the liver cytosol fractions acting on homologous nuclei whereas it is inhibited, in thymus nuclei, by the addition of thymus cytosol fractions.