Davies E, Bonnardeaux A, Plouin P F, Corvol P, Clauser E
INSERM U-36, Collège de France, Paris, France.
J Clin Endocrinol Metab. 1997 Feb;82(2):611-5. doi: 10.1210/jcem.82.2.3764.
Angiotensin II stimulates aldosterone secretion from the adrenal zona glomerulosa and mediates most of its biological effects via G protein-coupled type 1 angiotensin II receptors (AT1). A number of G protein-coupled receptors are constitutively activated as a result of somatic mutations in the gene encoding the protein. It is, therefore, possible that primary hyperaldosteronism caused by an aldosterone-producing adenoma (APA) may be the result of constitutive activation of the AT1 receptor. The 1.1-kilobase coding region (exon 5) of the AT1 receptor gene was analyzed in APA and normal adrenal tissue for the presence of mutations using single stranded conformational polymorphism and sequencing techniques. In 17 APAs, no functional mutations were found that could account for the observed pathophysiology. However, three silent polymorphisms were detected in regions encoding the second extracellular loop, the intracellular arm preceding the COOH terminal, and the 3'-untranslated region. In conclusion, somatic mutations in the coding region of the AT1 receptor gene do not appear to play a role in primary hyperaldosteronism caused by an APA.
血管紧张素II刺激肾上腺球状带分泌醛固酮,并通过G蛋白偶联的1型血管紧张素II受体(AT1)介导其大部分生物学效应。由于编码该蛋白的基因发生体细胞突变,许多G蛋白偶联受体被组成性激活。因此,由醛固酮生成腺瘤(APA)引起的原发性醛固酮增多症可能是AT1受体组成性激活的结果。使用单链构象多态性和测序技术分析了APA和正常肾上腺组织中AT1受体基因的1.1千碱基编码区(外显子5)是否存在突变。在17个APA中,未发现可解释观察到的病理生理学的功能性突变。然而,在编码第二个细胞外环、COOH末端之前的细胞内臂和3'-非翻译区的区域中检测到三个沉默多态性。总之,AT1受体基因编码区的体细胞突变似乎在由APA引起的原发性醛固酮增多症中不起作用。