McPhaul M J, Marcelli M, Zoppi S, Wilson C M, Griffin J E, Wilson J D
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8857.
J Clin Invest. 1992 Nov;90(5):2097-101. doi: 10.1172/JCI116093.
We have analyzed the nucleotide sequence of the androgen receptor from 22 unrelated subjects with substitution mutations of the hormone-binding domain. Eleven had the phenotype of complete testicular feminization, four had incomplete testicular feminization, and seven had Reifenstein syndrome. The underlying functional defect in cultured skin fibroblasts included individuals with absent, qualitative, or quantitative defects in ligand binding. 19 of the 21 substitution mutations (90%) cluster in two regions that account for approximately 35% of the hormone-binding domain, namely, between amino acids 726 and 772 and between amino acids 826 and 864. The fact that one of these regions is homologous to a region of the human thyroid hormone receptor (hTR-beta) which is a known cluster site for mutations that cause thyroid hormone resistance implies that this localization of mutations is not a coincidence. These regions of the androgen receptor may be of particular importance for the formation and function of the hormone-receptor complex.
我们分析了22名激素结合域存在替代突变的不相关受试者的雄激素受体核苷酸序列。其中11人具有完全性睾丸女性化表型，4人具有不完全性睾丸女性化表型，7人患有赖芬斯坦综合征。培养的皮肤成纤维细胞中的潜在功能缺陷包括配体结合存在缺失、定性或定量缺陷的个体。21个替代突变中的19个（90%）聚集在两个区域，这两个区域约占激素结合域的35%，即氨基酸726至772之间以及氨基酸826至864之间。这些区域之一与人甲状腺激素受体（hTR-β）的一个区域同源，而该区域是已知的导致甲状腺激素抵抗的突变聚集位点，这一事实表明突变的这种定位并非巧合。雄激素受体的这些区域可能对激素-受体复合物的形成和功能特别重要。
