Mu Y M, Takayanagi R, Imasaki K, Ohe K, Ikuyama S, Yanase T, Nawata H
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Clin Endocrinol (Oxf). 1998 Sep;49(3):301-6. doi: 10.1046/j.1365-2265.1998.00520.x.
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 GR alpha and GR beta mRNAs in the pituitary adenomas in six patients who were proven at surgery to have pituitary ACTH-producing adenomas.
Total RNA was extracted from six pituitary adenomas and pituitary tissue 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-PCR.
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 significantly different among the six adenomas.
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.
过夜8毫克地塞米松抑制试验常用于区分由垂体促肾上腺皮质激素（ACTH）分泌过多引起的库欣病与其他类型的库欣综合征。然而，少数产生ACTH的垂体腺瘤患者在给予8毫克地塞米松后血浆皮质醇无抑制。为了阐明垂体腺瘤中糖皮质激素受体（GR）水平与库欣病患者对地塞米松敏感性之间的关系，我们检测了6例经手术证实患有垂体ACTH分泌腺瘤患者垂体腺瘤中GRα和GRβ mRNA的水平。
从6个垂体腺瘤及其中一个腺瘤相邻的垂体组织中提取总RNA，通过定量逆转录聚合酶链反应（RT-PCR）检测这些样本中GRα、GRβ、阿黑皮素原（POMC）和β-肌动蛋白的mRNA水平。
对8毫克地塞米松抑制试验无反应的2例患者的腺瘤中GRα mRNA水平显著低于有反应的4例患者的腺瘤。GRβ mRNA水平远低于GRα mRNA水平，但6个腺瘤之间无显著差异。
这些结果强烈提示，垂体腺瘤中GRα表达降低可能是2例库欣病患者对8毫克地塞米松抑制试验明显不敏感的主要原因。
