Adrenocortical Zonation in Humans under Normal and Pathological Conditions
Adrenocortical Zonation in Humans under Normal and Pathological Conditions
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DOI：
10.1210/jc.2009-2010
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发表时间：
2010-05-01
影响因子：
5.8
通讯作者：
Mukai, Kuniaki
中科院分区：
文献类型：
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作者：
Nishimoto, Koshiro;Nakagawa, Ken;Mukai, Kuniaki
内容：醛固酮合成酶（CYP 11B 2）和类固醇11 β-羟化酶（CYP 11B 1）分别催化醛固酮和皮质醇合成的末端步骤，从而决定人肾上腺皮质细胞的功能分化。然而，关于正常和病理条件下表达这两种酶的细胞在肾上腺中的分布情况，目前还知之甚少。目的：本研究的目的是通过使用能够区分这两种酶的抗体来确定CYP 11 B2和-B1在人肾上腺标本中的定位。在正常情况下，CYP 11B 2是零星检测到的肾小球，而CYP 11B 1是完全检测到的束状网状带。肾上腺皮质细胞缺乏这两种酶观察外皮质区。除了传统的分区，我们发现了一个杂色的分区组成的包膜下细胞簇表达CYP 11B 2，我们称之为醛固酮生产细胞簇，和CYP 11B 1表达区。醛固酮生成腺瘤在表达CYP 11B 2的细胞群中彼此不同，而表达CYP 11B 1的细胞和双阴性细胞也混合在一起。库欣综合征患者的腺瘤完全表达CYP 11 B1，但不表达CYP 11 B2，导致萎缩的非肿瘤腺体。这两种类型的腺瘤的非肿瘤部分经常孔一个或多个醛固酮产生细胞簇，持续的条件下，抑制的肾素-血管紧张素system.Conclusion的CYP 11B 2的表达显着：CYP 11B 2和CYP 11B 1的人正常肾上腺皮质的免疫组化显示杂色带状细胞簇组成性表达CYP 11B 2。该技术可提供肾上腺皮质腺瘤的病理确诊。（临床内分泌代谢杂志95：2296-2305，2010）
Context: Aldosterone synthase (CYP11B2) and steroid 11 beta-hydroxylase (CYP11B1) catalyze the terminal steps for aldosterone and cortisol syntheses, respectively, thereby determining the functional differentiation of human adrenocortical cells. Little is known, however, about how the cells expressing the enzymes are actually distributed in the adrenals under normal and pathological conditions.Objective: The objective of the study was to determine the localization of CYP11B2 and -B1 in human adrenal specimens by using developed antibodies capable of distinguishing the two enzymes from each other.Results: Under normal conditions, CYP11B2 was sporadically detected in the zona glomerulosa, whereas CYP11B1 was entirely detected in the zonae fasciculata-reticularis. Adrenocortical cells lacking both enzymes were observed in the outer cortical regions. In addition to conventional zonation, we found a variegated zonation consisting of a subcapsular cell cluster expressing CYP11B2, which we termed aldosterone-producing cell cluster, and a CYP11B1-expressing area. Aldosterone-producing adenomas differed in cell populations expressing CYP11B2 from one another, whereas CYP11B1-expressing and double-negative cells were also intermingled. Adenomas from patients with Cushing's syndrome expressed CYP11B1 entirely but not CYP11B2, resulting in atrophic nontumor glands. The nontumor portions of both types of adenomas bore frequently one or more aldosterone-producing cell clusters, which sustained CYP11B2 expression markedly under the conditions of the suppressed renin-angiotensin system.Conclusion: Immunohistochemistry of the human normal adrenal cortex for CYP11B2 and CYP11B1 revealed a variegated zonation with cell clusters constitutively expressing CYP11B2. This technique may provide a pathological confirmatory diagnosis of adrenocortical adenomas. (J Clin Endocrinol Metab 95: 2296-2305, 2010)