Nakamura Yasuhiro, Maekawa Takashi, Felizola Saulo J A, Satoh Fumitoshi, Qi Xin, Velarde-Miranda Carolina, Plonczynski Maria W, Ise Kazue, Kikuchi Kumi, Rainey William E, Gomez-Sanchez Elise P, Gomez-Sanchez Celso E, Sasano Hironobu
Tohoku University Graduate School of Medicine, Department of Pathology, Sendai, Japan.
Tohoku University Hospital, Division of Nephrology and Hypertension, Sendai, Japan.
Mol Cell Endocrinol. 2014 Jul 5;392(1-2):73-9. doi: 10.1016/j.mce.2014.05.002. Epub 2014 May 14.
CYP11B1 and CYP11B2 play pivotal roles in adrenocorticosteroids synthesis. We performed semi-quantitative immunohistochemical analysis of these proteins in adrenals from patients with primary aldosteronism using novel monoclonal antibodies. Clusters of cortical cells positive for CYP11B2 were detected in the zona glomerulosa (ZG) of normal adrenal gland (NA), idiopathic hyperaldosteronism (IHA) and the adjacent adrenal of aldosterone-producing adenoma (APA). In APA, heterogenous immunolocalization of CYP11B2 and diffuse immunoreactivity of CYP11B1 were detected in tumor cells, respectively. The relative immunoreactivity of CYP11B2 in the ZG of adjacent adrenal of APA was significantly lower than that of NA, IHA and APA tumor cells, suggestive of suppressed aldosterone biosynthesis in these cells. These findings did indicate the regulatory mechanisms of aldosterone biosynthesis were different between normal/hyperplastic and neoplastic aldosterone-producing cells in human adrenals. CYP11B2 immunoreactivity in the ZG could also serve as a potential immunohistochemical marker differentiating morphologically hyperplastic ZG of IHA and APA adjacent adrenal.
细胞色素P450 11B1(CYP11B1)和细胞色素P450 11B2(CYP11B2)在肾上腺皮质类固醇合成中起关键作用。我们使用新型单克隆抗体对原发性醛固酮增多症患者肾上腺中的这些蛋白质进行了半定量免疫组织化学分析。在正常肾上腺(NA)、特发性醛固酮增多症(IHA)以及醛固酮瘤(APA)的相邻肾上腺的球状带(ZG)中检测到CYP11B2阳性的皮质细胞簇。在APA中,分别在肿瘤细胞中检测到CYP11B2的异质性免疫定位和CYP11B1的弥漫性免疫反应性。APA相邻肾上腺ZG中CYP11B2的相对免疫反应性显著低于NA、IHA和APA肿瘤细胞,提示这些细胞中醛固酮生物合成受到抑制。这些发现确实表明,人肾上腺中正常/增生性和肿瘤性醛固酮产生细胞之间醛固酮生物合成的调节机制不同。ZG中CYP11B2免疫反应性也可作为区分IHA和APA相邻肾上腺形态学增生性ZG的潜在免疫组织化学标志物。