Ebisawa Takanori, Tojo Katsuyoshi, Tajima Naoko, Kamio Masami, Oki Yutaka, Ono Katsuhiko, Sasano Hironobu
Division of Diabetes and Endocrinology, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo 105-8461, Japan.
Endocr Pathol. 2008 Winter;19(4):252-60. doi: 10.1007/s12022-008-9052-0.
Subclinical Cushing's disease (SCD) is characterized by lack of clinically evident Cushingoid features, despite abnormal hypersecretion of ACTH. Nearly half the cases of SCD are due to macroadenomas, and in the majority of them, ACTH secretion is not inhibited even by high-dose dexamethasone. Impaired glucocorticoid (GC) action may be correlated with the proliferation and development of pituitary macroadenomas causing SCD. In this study, immunohistochemical analysis of the resected tumors were performed to evaluate the expression of 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) and glucocorticoid receptor (GR) in pituitary tissues obtained from two SCD (macroadenomas), eight Cushing's disease (CD) (microadenomas), nine acromegaly, and nine normal pituitary (NP). Scattered 11betaHSD2-immunopositive cells were detected in all NP tissues, but its immunoreactivity was totally absent in any tumorous tissues except two CD. Scattered GR-immunopositive cells were also detected and GR immunostaining was restricted to the cytosol in NP tissue. In contrast, GR-immunopositive cells were abundantly present and GR immunostaining was restricted to the nucleus in all the tumorous tissues. There were marked differences in both expression levels and localization between NP tissues and all the tumors. There may be a mechanism other than that via 11betaHSD2 for causes of impaired negative feedback action by GC in SCD and CD, but results of our present study suggest that impaired GC action may be involved, at least in part, in tumorigenesis of SCD and CD.
亚临床库欣病（SCD）的特征是，尽管促肾上腺皮质激素（ACTH）分泌异常增多，但缺乏明显的库欣样临床特征。近一半的SCD病例由大腺瘤引起，并且在大多数此类病例中，即使给予高剂量地塞米松，ACTH分泌也不会受到抑制。糖皮质激素（GC）作用受损可能与导致SCD的垂体大腺瘤的增殖和发展相关。在本研究中，对切除的肿瘤进行了免疫组织化学分析，以评估11β-羟类固醇脱氢酶2型（11βHSD2）和糖皮质激素受体（GR）在取自两名SCD患者（大腺瘤）、八名库欣病（CD）患者（微腺瘤）、九名肢端肥大症患者以及九个正常垂体（NP）的垂体组织中的表达情况。在所有NP组织中均检测到散在的11βHSD2免疫阳性细胞，但除两名CD患者外，在任何肿瘤组织中均未检测到其免疫反应性。也检测到了散在的GR免疫阳性细胞，并且在NP组织中GR免疫染色仅限于细胞质。相比之下，在所有肿瘤组织中GR免疫阳性细胞大量存在，并且GR免疫染色仅限于细胞核。NP组织与所有肿瘤组织在表达水平和定位上均存在显著差异。在SCD和CD中，GC负反馈作用受损的原因可能存在除通过11βHSD2之外的其他机制，但我们目前的研究结果表明，GC作用受损可能至少部分参与了SCD和CD的肿瘤发生过程。
