Vassart G
Institut de Recherche Interdisciplinaire, Université Libre de Bruxelles, Belgium.
Horm Res. 1997;48 Suppl 4:47-50. doi: 10.1159/000191313.
From the analysis of accumulated data about adrenergic receptors, it was hypothesized that some mutations within the thyroid-stimulating hormone (TSH) receptor would activate it constitutively. As TSH positively controls the function, differentiation and growth of thyrocytes by cyclic AMP-dependent mechanisms, such somatic or germline mutations would cause readily identifiable phenotypes in the form of monoclonal hyperfunctional benign tumours or hereditary dominant hyperthyroidism, respectively. This hypothesis turned out to be correct: of 29 hyperfunctioning adenomas, 23 were found to have a mutation at various positions of the serpentine portion of the TSH receptor. In five families with autosomal dominant hyperthyroidism and one sporadic case, five additional different mutations were identified. Altogether, 20 different residues have been found mutated in toxic adenomas or toxic thyroid hyperplasia. It is tempting to speculate that as the TSH receptor is already 'noisy' in its wild-type state, it would be more readily activated by mutations than others.
通过对肾上腺素能受体累积数据的分析，推测促甲状腺激素（TSH）受体内的某些突变会使其组成性激活。由于TSH通过环磷酸腺苷（cAMP）依赖机制正向调控甲状腺细胞的功能、分化和生长，这种体细胞或种系突变将分别以单克隆高功能良性肿瘤或遗传性显性甲状腺功能亢进的形式导致易于识别的表型。这一假设被证明是正确的：在29个高功能腺瘤中，发现23个在TSH受体蛇形部分的不同位置存在突变。在5个常染色体显性甲状腺功能亢进家族和1个散发病例中，又鉴定出另外5种不同的突变。在毒性腺瘤或毒性甲状腺增生中总共发现20个不同的残基发生了突变。人们不禁推测，由于TSH受体在野生型状态下就已经“嘈杂”，它比其他受体更容易被突变激活。
