The aim of the study was to identify cell cycle regulatory genes that are regulated by GCs and the glucocorticoid receptor and to assess regulatory genes that have a rate-limiting action on corticotrope proliferation and may be disregulated in CD.
These results suggest that the pathogenesis of Cushing disease caused by overexpression of heat shock proteins and consequently misregulated GR sensitivity may be overcome pharmacologically with an appropriate HSP90 inhibitor.
Fifty-two patients with active CS (38 Cushing's disease and 14 with cortisol-secreting adrenal adenoma) were genotyped for GR polymorphisms (BclI, N363S, ER22/23EK, and A3669G).
Our aim was to analyze the association of NR3C1 and HSD11B1 gene variants with the severity of some clinical and hormonal features of Cushing's disease.
Rare cases of human glucocorticoid receptor (hGRalpha) (NR3C1) gene mutations have been described in the gemline or somatic state in Cushing's disease (CD).
Previous studies have demonstrated that the genetic variations of glucocorticoid receptor gene (NR3C1) are associated with both familial steroid resistance and acquired steroid resistance in some diseases, such as Cushing's disease, leukemia, lupus nephritis, and female pseudohermaphroditism.
We found that somatic mutations of the GR gene are not a frequent cause of relative CR in these cells, but our observations indicate that loss of heterozygosity (LOH) at the GR gene locus is a relativity frequent phenomenon in pituitary adenomas of patients with Cushing's disease.
We screened for the GR gene in leukocyte and tumor DNA from 22 patients with Cushing's disease for mutations using PCR/single strand conformation polymorphism analysis.
These results suggest strongly that decreased expression of GR alpha in pituitary adenomas may be the major reason for the marked insensitivity to the 8-mg dexamethasone suppression test observed in two patients with Cushing's disease.
We have hypothesized that abnormalities of the glucocorticoid receptor (GR) gene might play a role in the development of Cushing's disease via an increase in the relative production of the nonligand-binding splice variant of the GR, GR beta, known to exert dominant negative effects over the ligand-binding isoform, GR alpha.