Department of Physiology, Medical College of Georgia, 1120 15th Street, Augusta, Georgia 30912, USA.
Eur J Endocrinol. 2011 Apr;164(4):613-9. doi: 10.1530/EJE-10-1085. Epub 2011 Jan 19.
Primary aldosteronism (PA) is the most common form of endocrine hypertension affecting ∼8-10% of hypertensive subjects. Aldosterone production in PA occurs under low-renin conditions, and the mechanisms that maintain the production of aldosterone in PA remain unknown. Objective This study was designed to compare the transcript profiles between aldosterone-producing adenoma (APA) and their adjacent adrenal gland (AAG) from the same adrenal.
Total RNA was extracted from ten APA and ten AAG; and subsequently analyzed by microarray and real-time quantitative RT-PCR (qPCR). The microarray data were paired for each APA-AAG, and analyzed by GeneSpring GX 11 with paired t-test and fold change calculations for each transcript. Changes identified by microarray analysis were confirmed by qPCR.
Microarray analysis indicated that 14 genes had significantly up-regulated expression in APA compared to AAG. Among the elevated genes were aldosterone synthase (CYP11B2) as well as novel transcription factors, calmodulin-binding proteins, and other genes that have not been previously studied in APA. Selective analysis of 11 steroidogenic enzymes using microarray demonstrated that only CYP11B2 showed a significantly higher transcript level in APA compared to AAG (P<0.001). In contrast, AKR1C3 (17β-hydroxysteroid dehydrogenase type 5), CYP17 (17α-hydroxylase/17,20 lyase), and CYB5 (cytochrome b5) showed significantly lower transcript level in APA (P<0.05).
The transcriptome analysis of APA compared with AAG showed several novel genes that are associated with APA phenotype. This gene list provides new candidates for the elucidation of the molecular mechanisms leading to PA.
原醛症（PA）是影响 8-10%高血压患者的最常见内分泌性高血压类型。PA 中的醛固酮产生发生在低肾素条件下，而维持 PA 中醛固酮产生的机制尚不清楚。目的 本研究旨在比较来自同一肾上腺的醛固酮分泌腺瘤（APA）与其相邻肾上腺组织（AAG）之间的转录谱。
从 10 例 APA 和 10 例 AAG 中提取总 RNA；随后通过微阵列和实时定量 RT-PCR（qPCR）进行分析。对每个 APA-AAG 进行微阵列数据配对，并使用 GeneSpring GX 11 通过配对 t 检验和每个转录本的倍数变化进行分析。通过 qPCR 验证微阵列分析确定的变化。
微阵列分析表明，与 AAG 相比，APA 中有 14 个基因的表达明显上调。在升高的基因中，有醛固酮合酶（CYP11B2）以及钙调蛋白结合蛋白等新型转录因子和其他以前在 APA 中未研究过的基因。使用微阵列对 11 种类固醇生成酶的选择性分析表明，与 AAG 相比，仅 CYP11B2 在 APA 中的转录本水平显著更高（P<0.001）。相比之下，AKR1C3（17β-羟甾脱氢酶类型 5）、CYP17（17α-羟化酶/17,20 裂解酶）和 CYB5（细胞色素 b5）在 APA 中的转录本水平显著较低（P<0.05）。
APA 与 AAG 相比的转录组分析显示了与 APA 表型相关的几个新基因。该基因列表为阐明导致 PA 的分子机制提供了新的候选基因。
