THE GLUCOCORTICOID RECEPTORS ARE IN MITOCHONDRIA

The next step is to focus on the research that shows why glucocorticoid receptors are vulnerable to mitochondrial neurotoxins. The articles cited below indicate this vulnerability is due to their location in the mitochondria of the cell.
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: IUBMB Life. 2008 Apr;60(4):210-23.
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Steroid and thyroid hormone receptors in mitochondria.Psarra AM, Sekeris CE.Biomedical Research Foundation, Academy of Athens, Center for Basic Research, Athens, Greece.Receptors for glucocorticoids, estrogens, androgens, and thyroid hormones have been detected in mitochondria of various cell types by Western blotting, immunofluorescence labeling, confocal microscopy, and immunogold electron microscopy. A role of these receptors in mitochondrial transcription, OXPHOS biosynthesis, and apoptosis is now being revealed. Steroid and thyroid hormones regulate energy production, inducing nuclear and mitochondrial OXPHOS genes by way of cognate receptors. In addition to the action of the nuclearly localized receptors on nuclear OXPHOS gene transcription, a parallel direct action of the mitochondrially localized receptors on mitochondrial transcription has been demonstrated. The coordination of transcription activation in nuclei and mitochondria by the respective receptors is in part realized by their binding to common trans acting elements in the two genomes. Recent evidence points to a role of the mitochondrial receptors in cell survival .....
2: Semin Reprod Med. 2007 May;25(3):154-64.
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Actions of steroids in mitochondria.Gavrilova-Jordan LP, Price TM.Division of Reproductive Endocrinology and Fertility, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, USA.Investigations of indirect and direct actions of steroids on the mitochondria are relatively new areas of research. In this review we provide brief background information regarding mitochondrial structure and function and then focus upon interactions of glucocorticoid, estrogen, androgen, and progesterone receptors with mitochondria. We evaluate the current evidence for steroid receptor localization in the mitochondria based on techniques of Western blot analysis, immunocytochemistry, electron microscopy, and mass spectrometry..... These interactions may play a role in mitochondrial-dependent processes of oxidative phosphorylation and apoptosis. Physiological examples of these interactions are discussed.
3: Mol Cell Endocrinol. 2003 Nov 14;209(1-2):51-60.
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The dynamic localization of the glucocorticoid receptor in rat C6 glioma cell mitochondria.Koufali MM, Moutsatsou P, Sekeris CE, Breen KC.Department of Psychiatry, Ninewells Hospital, University of Dundee Medical School, Dundee, DD1 9SY, UK.Glucocorticoids modify gene expression via the translocation of receptors from the cytosol to the nucleus following agonist-associated receptor activation. In this study, we have characterized mitochondrial glucocorticoid (GR) localization and associated translocation kinetics in the C6 mouse glioma cell line. Treatment of the cells, which were cultured in steroid-depleted culture medium, with the GR agonist dexamethasone (dex) resulted in a dramatic decrease in mitochondrial GR levels in parallel with those of the cytosolic receptor. The effect was not observed in isolated intact mitochondria suggesting that the effect is unlikely to be direct but is rather a component of the combined cellular response to GR activation. A marked stimulation of the expression of the mitochondrially-encoded cytochrome oxidase-1 (COX-1) gene was found following GR activation and its export from mitochondria. The effects were inhibited by RU486. Therefore, GR is likely to have a functional role at the level of the mitochondria within intact cells.