Mitochondrial localization of glucocortocoid receptor in glial (Muller) cells in the salamander retina

Glucocorticoid hormones regulate the transcription of nuclear genes by way of their receptors. In addition, these hormones modulate mitochondrial gene transcription by mechanisms that remain poorly understood. Using immunofluorescence labeling in isolated Muller and photoreceptor cells and in intact salamander retina, we found that the glucocorticoid receptor (GR) is localized in both cell types. Confocal laser scanning microscopy and double staining with cytochrome oxidase (COX) showed that GR is localized in the mitochondria of Muller cells, but not in the mitochondria of photoreceptors. GR also colocalizes with glutamine synthetase (GS) in the cytoplasm of Muller cells. GR is also localized in the microvilli of the distal process of Muller cells and in the synaptic terminal of photoreceptors. Pre-incubation of Muller cells with 1 muM dexamethasone (DEX) for 7 h led to greater than 50% inhibition of the glutamate-induced increase in mitochondrial NADH. This late effect of glucocorticoids on glutamate metabolism could be ascribed, in part, to a direct action of steroid hormones on mitochondrial. metabolism. (C) 2003 Wiley-Liss, Inc

Localization of the glucocorticoid receptor in rat brain mitochondria

The distribution of glucocorticoid receptor in subcellular fractions of brain cortex and hippocampus, two regions rich in glucocorticoid receptor, has revealed its presence in nuclei, cytosol, mitochondria, synaptosomes, and synaptosomal mitochondria, The identification of glucocorticoid receptor has been accomplished both by Western blotting using antibodies recognizing the carboxy and the amino terminus of the glucocorticoid receptor and by immunogold electron microscopy using the same anti-glucocorticoid receptor antibodies. Antibody-glucocorticoid receptor interaction is abolished by preincubation of each antibody with its competing peptide. In addition to the intact 95-kDa glucocorticoid receptor in all fractions, lower molecular weight glucocorticoid receptor fragments have been also detected by Western blotting. The presence of glucocorticoid receptor in brain mitochondria supports the concept of a direct action of glucocorticoids on mitochondrial gene transcription, parallel to the established primary actions of the hormones on nuclear gene transcription, as a mechanism of coordinate regulation of respiratory enzyme biosynthesis by steroid hormones. (C) 2001 Academic Press