Low level of glucocorticoid receptor messenger ribonucleic acid in pituitary adenomas manifesting Cushing's disease with resistance to a high dose-dexamethasone suppression test

• Published in: Clinical endocrinology (Oxford) 1998-09, Vol.49 (3), p.301-306
• Main Authors: Mu, Yi-Ming, Takayanagi, Ryoichi, Imasaki, Kyosuke, Ohe, Kenji, Ikuyama, Shoichiro, Yanase, Toshihiko, Nawata, Hajime
• Format: Article
• Language: English
• Subjects: Actins - genetics; Adenoma - chemistry; Adenoma - metabolism; Adrenocorticotropic Hormone - metabolism; Adult; Biological and medical sciences; Cushing Syndrome - diagnosis; Cushing Syndrome - etiology; Dexamethasone; Endocrinopathies; Female; Glucocorticoids; Humans; Hypothalamus. Hypophysis. Epiphysis (diseases); Male; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Pituitary Function Tests; Pituitary Neoplasms - chemistry; Pituitary Neoplasms - metabolism; Predictive Value of Tests; Pro-Opiomelanocortin - genetics; Receptors, Glucocorticoid - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1046/j.1365-2265.1998.00520.x

OBJECTIVES The overnight 8‐mg dexamethasone suppression test is often used to differentiate Cushing's disease, due to an oversecretion of ACTH from the pituitary gland, from other kinds of Cushing's syndrome. However, a few patients with ACTH‐producing pituitary adenoma show no suppression of plasma cortisol after the administration of 8 mg of dexamethasone. To clarify the relationship between the level of glucocorticoid receptor (GR) in the pituitary adenoma and the sensitivity to dexamethasone in Cushing's disease, we thus examined the levels of GRα and GRβ mRNAs in the pituitary adenomas in six patients who were proven at surgery to have pituitary ACTH‐producing adenomas. MATERIALS Total RNA was extracted from six pituitary adenomas and pituitary tissue adjacent to one of the adenomas, and the mRNA levels of GRα, GRβ, pro‐opiomelanocortin (POMC) and β‐actin in these samples were sampled by quantitative RT–PCR. RESULTS The GRα mRNA levels in the adenomas from the two patients who showed no response to the 8‐mg dexamethasone suppression test were significantly lower than those in the adenomas of four patients who showed suppression. The GRβ mRNA level was much lower than that of GRα mRNA but not significantly different among the six adenomas. CONCLUSIONS These results suggest strongly that decreased expression of GRα 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.