Bassett Mary H, Mayhew Bobbie, Rehman Khurram, White Perrin C, Mantero Franco, Arnaldi Giorgio, Stewart Paul M, Bujalska Iwona, Rainey William E
Divisions of Reproductive and Pediatric Endocrinology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032, USA.
J Clin Endocrinol Metab. 2005 Sep;90(9):5446-55. doi: 10.1210/jc.2005-0836. Epub 2005 Jun 28.
Excess production of aldosterone or cortisol has profound effects on cardiovascular function and impacts other major organ systems. The mechanisms leading to the autonomous hypersecretion of aldosterone or cortisol in aldosterone-producing adenoma (APA) or cortisol-producing adenoma (CPA) are unknown.
The objective of this study was to compare the expression profiles of several steroid-metabolizing enzymes and transcription factors from normal adrenal (NA), APAs, and CPAs.
RNA from NAs, APAs, and CPAs were analyzed by microarray and real-time RT-PCR.
This study was performed at academic research laboratories.
At least nine normal controls and 12 patients with APA or CPA were studied.
There was no intervention procedure.
The main outcome measure was the expression of steroidogenic enzymes in adrenocortical disease.
A microarray indicated a greater than 3-fold increase in the expression of CYP11B2 (aldosterone synthase) in APA, whereas 11beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) and HSD17B1 had greater than 3-fold increases in expression in CPA compared with NA. Real-time RT-PCR showed that APAs produced higher levels of HSD3B2, CYP21 (21-hydroxylase), and CYP11B2 mRNA, whereas CPAs produced higher levels of CYP11A (cholesterol side-chain cleavage), CYP17 (17alpha-hydroxylase/17-20 lyase), HSD3B2, and CYP11B1 (11beta-hydroxylase) mRNA compared with normal adrenal. Steroidogenic factor-1, DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome gene 1), and GATA-6 were expressed at higher levels in APAs and CPAs, whereas NURR1 was expressed at higher levels in APAs than in CPAs or NAs.
Elevated production of aldosterone in APAs and of cortisol in CPAs is associated with increased expression of enzymes needed for corticosteroid production along with alterations in transcription factors that enhance the expression of steroid-metabolizing enzymes.
醛固酮或皮质醇分泌过多对心血管功能有深远影响，并会影响其他主要器官系统。导致醛固酮瘤（APA）或皮质醇瘤（CPA）中醛固酮或皮质醇自主分泌过多的机制尚不清楚。
本研究的目的是比较正常肾上腺（NA）、APA和CPA中几种类固醇代谢酶和转录因子的表达谱。
通过微阵列和实时逆转录聚合酶链反应分析NA、APA和CPA中的RNA。
本研究在学术研究实验室进行。
至少研究了9名正常对照者以及12名患有APA或CPA的患者。
未进行干预程序。
主要观察指标是肾上腺皮质疾病中类固醇生成酶的表达。
微阵列显示，与NA相比，APA中CYP11B2（醛固酮合酶）的表达增加了3倍以上，而2型11β-羟基类固醇脱氢酶（HSD11B2）和HSD17B1在CPA中的表达增加了3倍以上。实时逆转录聚合酶链反应显示，与正常肾上腺相比，APA产生更高水平的HSD3B2、CYP21（21-羟化酶）和CYP11B2 mRNA，而CPA产生更高水平的CYP11A（胆固醇侧链裂解酶）、CYP17（17α-羟化酶/17-20裂解酶）、HSD3B2和CYP11B1（11β-羟化酶）mRNA。类固醇生成因子-1、DAX-1（剂量敏感性性别反转、先天性肾上腺发育不全、X染色体基因1关键区域）和GATA-6在APA和CPA中的表达水平较高，而NURR1在APA中的表达水平高于CPA或NA。
APA中醛固酮生成增加以及CPA中皮质醇生成增加与皮质类固醇生成所需酶的表达增加以及增强类固醇代谢酶表达的转录因子改变有关。
