We have characterized the gene for the mouse glucocorticoid receptor. The gene spans approximately 110 kilobases, and glucocorticoid receptor transcripts are assembled from nine exons. Expression of the gene is controlled by at least three promoters, resulting in glucocorticoid receptor transcripts with different 5' nontranslated exons. One promoter is cell-specific, found to be active only in ...

A DNA fragment containing glucocorticoid receptor binding sites in the mouse mammary tumor virus promoter was reconstituted in vitro with histones to form nucleosome cores, which become positioned on the DNA fragment in a sequence-specific manner. Glucocorticoid receptor binding to specific DNA sequences was analyzed by quantitative DNase I footprinting. The receptor interacted with surprisingl...

We used a whole-cell glucocorticoid receptor assay to examine characteristics of the glucocorticoid receptor in the lymphocytes of normal human donors. We measured binding of [3H]dexamethasone to the lymphocytes of four different donors on several different occasions; the variation about the mean for the assays was +/- 15%. Whole-cell assays in 15 normal subjects showed a mean value of 6.18 fmo...

The glucocorticoid receptor and the mineralocorticoid receptor are hormone-dependent transcription factors. They regulate the excitability of rat hippocampus CA1 neurons in a coordinated fashion. We studied the spatial distribution of these transcription factors in nuclei of CA1 neurons by dual labeling immunocytochemistry and confocal microscopy, combined with novel image restoration and image...

The over-expression of NF-κB signalling in both muscle and immune cells contribute to the pathology in dystrophic muscle. The anti-inflammatory properties of glucocorticoids, mediated predominantly through monomeric glucocorticoid receptor inhibition of transcription factors such as NF-κB (transrepression), are postulated to be an important mechanism for their beneficial effects in Duchenne mus...

2 Summary Prolonged exposure to glucocorticoid stress hormones precipitates mood and cognitive disorders. We identified arginine and glutamate rich 1 (ARGLU1) in a screen for new modulators of glucocorticoid signaling in the CNS. Biochemical studies found that the glutamate rich C-terminus coactivates the glucocorticoid receptor (GR) and the arginine rich N-terminus interacts with splicing fact...

Glucocorticoid hormones (GCs) are used to treat a variety of diseases because of their potent anti-inflammatory effect and their ability to induce apoptosis in lymphoid malignancies through the glucocorticoid receptor (GR). Despite ongoing research, high glucocorticoid efficacy and widespread usage in medicine, resistance, disease relapse and toxicity remain factors that need addressing. Unders...

PURPOSE To determine the cellular mechanism of action of the intraocular pressure (IOP) lowering steroid tetrahydrocortisol (THF). METHODS Tetrahydrocortisol was evaluated for glucocorticoid antagonist activity using in vitro and in vivo assays. Systemically administered THF was evaluated for its ability to inhibit dexamethasone-induced body weight loss and systemic hypertension in rats. In v...

Glucocorticoids precociously induce fetal rat UGT1A6 and potentiate polycyclic aromatic hydrocarbon (PAH)-dependent induction of this enzyme in vivo and in isolated rat hepatocytes. To establish whether induction was due to glucocorticoid receptor (GR), luciferase reporter vectors were tested in transfection assays with HepG2 cells. Using a reporter construct containing approximately 2.26 kilob...

These studies further evaluated the relative role of mineralocorticoid (type I) and glucocorticoid (type II) receptors in mediating corticosteroid feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Acute treatment of rats with the selective mineralocorticoid receptor antagonist, RU28318 (50 mg/kg sc), produced elevated basal corticosterone levels in the morning, but had no ef...