Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma.
Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma.
复制标题
DOI：
10.1097/md.0000000000003659
复制
发表时间：
2016-05
期刊：
影响因子：
1.6
通讯作者：
Kohno N
中科院分区：
文献类型：
--
作者：
Kishimoto R;Oki K;Yoneda M;Gomez-Sanchez CE;Ohno H;Kobuke K;Itcho K;Kohno N
我们的目的是检测与G蛋白偶联受体（GPCR）在醛固酮产生腺瘤（阿帕）的新基因，并阐明醛固酮产生的机制。使用无已知突变的APA（APA-WT）样品（n = 3）和具有KCNJ 5突变的阿帕（APA-KCNJ 5; n = 3）进行靶向GPCR相关基因的微阵列分析。 由于促性腺激素释放激素受体（GNRHR）是最高的表达在APA-WT通过芯片分析，我们研究促性腺激素释放激素（GnRH）刺激对醛固酮的生产。定量聚合酶链反应检测结果显示，APA-WT组GNRHR表达水平高于APA-KCNJ 5组（P <0.05）。 APA-WT组LHCGR表达水平明显升高，且所有阿帕组GNRHR与LHCGR表达水平均呈正相关（r = 0.476，P <0.05）。 APA-WT组（n = 9）GNRHR和LHCGR水平均高于APA-KCNJ 5组（n = 13），其促肾上腺皮质激素释放激素（GnRH）反应性显著高于APA-KCNJ 5组（P <0.05）。 多元回归分析显示KCNJ 5突变与GNRHR mRNA表达相关（β = 0.94，P <0.01）。 KCNJ 5基因T158 A突变的HAC 15细胞GNRHR表达水平明显低于对照组（P <0.05）。 我们阐明了在APA-WT中GNRHR和LHCGR的表达增加，以及包括与GnRH刺激的临床结果相关的受体表达的分子分析。
Supplemental Digital Content is available in the text We aimed to detect novel genes associated with G protein-coupled receptors (GPCRs) in aldosterone-producing adenoma (APA) and elucidate the mechanisms underlying aldosterone production. Microarray analysis targeting GPCR-associated genes was conducted using APA without known mutations (APA-WT) samples (n = 3) and APA with the KCNJ5 mutation (APA-KCNJ5; n = 3). Since gonadotropin-releasing hormone receptor (GNRHR) was the highest expression in APA-WT by microarray analysis, we investigated the effect of gonadotropin-releasing hormone (GnRH) stimulation on aldosterone production. The quantitative polymerase chain reaction assay results revealed higher GNRHR expression levels in APA-WT samples those in APA-KCNJ5 samples (P < 0.05). LHCGR levels were also significantly elevated in APA-WT samples, and there was a significant and positive correlation between GNRHR and LHCGR expression in all APA samples (r = 0.476, P < 0.05). Patients with APA-WT (n = 9), which showed higher GNRHR and LHCGR levels, had significantly higher GnRH-stimulated aldosterone response than those with APA-KCNJ5 (n = 13) (P < 0.05). Multiple regression analysis revealed that the presence of the KCNJ5 mutation was linked to GNRHR mRNA expression (β = 0.94 and P < 0.01). HAC15 cells with KCNJ5 gene carrying T158A mutation exhibited a significantly lower GNRHR expression than that in control cells (P < 0.05). We clarified increased expression of GNRHR and LHCGR in APA-WT, and the molecular analysis including the receptor expression associated with clinical findings of GnRH stimulation.