The expression of glucocorticoid and mineralocorticoid receptors in pituitary tumors causing Cushing's disease and silent corticotroph tumors

Pituitary neuroendocrine corticotroph tumors commonly cause Cushing's disease (CD) that results from increased adrenocorticotropic hormone (ACTH) secretion by the pituitary tumor and consequent increase of cortisol levels in blood. However, in some patients, corticotroph tumors remain clinically non-functioning. Cortisol secretion is regulated by the hypothalamic-pituitary-adrenal axis and includes a negative feedback between cortisol and ACTH secretion. Glucocorticoids reduce ACTH level both by hypothalamic regulation and acting on corticotrophs glucocorticoid (GR) and mineralocorticoid (MR) receptors. The aim of the study was to determine the role of GR and MR expression at mRNA and protein levels in both functioning and silent corticotroph tumors. Ninety-five patients were enrolled, including 70 with CD and 25 with silent corticotroph tumors. Gene expression levels of and coding for GR and MR, respectively, were determined with qRT-PCR in the two tumor types. GR and MR protein abundance was assessed with immunohistochemistry. Both GR and MR were expressed in corticotroph tumors. Correlation between and expression levels was observed. expression was higher in silent than in functioning tumors. In CD patients and levels were negatively correlated with morning plasma ACTH levels and tumor size. Higher was confirmed in patients with remission after surgery and in densely granulated tumors. Expression of both genes and GR protein was higher in -mutated tumors. Similar relationship between mutations and expression levels were observed in analysis of silent tumors that also revealed a negative correlation between GR and tumor size and higher expression in densely granulated tumors. Although the associations between gene/protein expression and patients clinical features are not strong, they consistently show an evident trend in which higher receptor expression corresponds to more favorable clinical characteristics.