To evaluate the effects of glucocorticoid receptor (GR) polymorphisms (BclI, N363S, ER22/23EK and A3669G) which influence peripheral glucocorticoid sensitivity on muscular function in endogenous CS.
Steroidogenesis inhibitors, centrally acting agents, and glucocorticoid receptor antagonists are currently available to treat hypercortisolism, and several novel agents are in development.
We hypothesized that HDAC inhibition (HDACi) decreased transcriptional activity of glucocorticoid receptor (GR), which ameliorates hypertension and hyperglycemia in patients with CS.
Mifepristone, a glucocorticoid receptor antagonist, can be used to manage hypercortisolism in patients with ectopic adrenocorticotropic hormone syndrome (EAS) when surgical cure is not feasible.
We hypothesized that histone deacetylase inhibitors (HDACi) could attenuate hepatic steatosis through glucocorticoid receptor (GR) acetylation in experimental CS.
Optimization of the previously described fused azadecalin series of selective GR antagonists led to the identification of CORT125134, which is currently being evaluated in a phase 2 clinical study in patients with Cushing's syndrome.
Three novel heterozygous missense NR3C1 mutations (R477S, Y478C, and L672P) were identified in patients presenting with adrenal incidentalomas, glucocorticoid excess without Cushing syndrome.
We investigate the role of gender, disease etiology, duration, and degree of hypercortisolism as well as the impact of glucocorticoid receptor (GR) polymorphisms on the development of bone complications in CS.
In this study, polymorphisms in the 11βHSD1 and NR3C1 genes were associated with impaired cognitive function, indicating that GC sensitivity and prereceptor regulation of GC action may play a role in the long-term consequences of CS.
Lack of mutations in the gene coding for the hGR (NR3C1) in a pediatric patient with ACTH-secreting pituitary adenoma, absence of stigmata of Cushing's syndrome and unusual histologic features.
The A3669G polymorphism of the GR gene plays a protective role in patients with CS, attenuating the effects of GC excess on glucose metabolism as shown by their reduced risk of diabetes.
We propose thus that GR haploinsufficiency compromises glucocorticoid sensitivity and may represent a novel genetic cause of subclinical hypercortisolism, incidentally revealed bilateral adrenal hyperplasia and mineralocorticoid-independent hypertension.
Interindividual variations in glucocorticoid sensitivity have been associated with manifestations of cortisol excess or deficiency and may be partly explained by polymorphisms in the human glucocorticoid receptor (hGR) gene.