LOW-LEVEL OF GLUCOCORTICOID RECEPTOR MESSENGER-RIBONUCLEIC-ACID IN PITUITARY-ADENOMAS MANIFESTING CUSHINGS-DISEASE WITH RESISTANCE TO A HIGH-DOSE DEXAMETHASONE SUPPRESSION TEST

OBJECTIVES The overnight 8-mg dexamethasone suppression test is often used to differentiate Cushing's disease, due to an oversecretion of AC TH from the pituitary gland, from other kinds of Gushing's syndrome, H owever, a few patients with ACTH-producing pituitary adenoma show no s uppression of plasma cortisol after the administration of 8 mg of dexa methasone. To clarify the relationship between the level of glucocorti coid receptor (GR) in the pituitary adenoma and the sensitivity to dex amethasone in Gushing's disease, we thus examined the levels of GR alp ha and GR beta mRNAs in the pituitary adenomas in six patients who wer e proven at surgery to have pituitary ACTH-producing adenomas, MATERIA LS Total RNA was extracted from six pituitary adenomas and pituitary t issue adjacent to one of the adenomas, and the mRNA levels of GR alpha , GR beta, pro-opiomelanocortin (POMC) and beta-actin in these samples were sampled by quantitative RT-PGR. RESULTS The GR alpha 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 GR beta mRNA level was much lower than that of GR alpha mRNA but not significa ntly different among the six adenomas, CONCLUSIONS These results sugge st strongly that decreased expression of GR alpha in pituitary adenoma s may be the major reason for the marked insensitivity to the 8-mg dex amethasone suppression test observed in two patients with Gushing's di sease.