Imasaki K, Hasegawa T, Okabe T, Sakai Y, Haji M, Takayanagi R, Nawata H
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Eur J Endocrinol. 1994 Jun;130(6):569-74. doi: 10.1530/eje.0.1300569.
We have characterized the androgen receptor in a Japanese girl and her maternal cousin in a family with incomplete androgen insensitivity syndrome, and have investigated the molecular basis. Whole-cell androgen binding assay in cultured genital skin fibroblasts from both patients showed a normal maximum binding capacity and a normal apparent dissociation constant. However, androgen binding in fibroblasts from both patients decreased to 30% when the assay temperature was raised from 30 degrees C to 41 degrees C, indicating the presence of the thermolability of ligand binding to the androgen receptor. Sequence analysis of the coding exons of the androgen receptor gene from the patients revealed a single nucleotide substitution at position 2881 in exon G, resulting in the conversion of arginine (CGT) to histidine (CAT) at amino acid position 840 in the hormone-binding domain of the androgen receptor. The family study showed that the mothers and the maternal grandmother of the patients are heterozygous carriers for this mutation, whereas the father does not carry it, supporting the view that androgen insensitivity syndrome is an X chromosome-linked disorder. The single amino acid substitution may explain the qualitative abnormality of the androgen receptor displaying thermolability, which is thought to be the pathogenesis of incomplete androgen insensitivity syndrome in the patients.
我们对一名患有不完全雄激素不敏感综合征的日本女孩及其母系表亲的雄激素受体进行了特征分析，并研究了其分子基础。对两名患者培养的生殖器皮肤成纤维细胞进行的全细胞雄激素结合试验显示，最大结合能力正常，表观解离常数也正常。然而，当试验温度从30℃升至41℃时，两名患者成纤维细胞中的雄激素结合下降至30%，这表明配体与雄激素受体结合存在热稳定性。对患者雄激素受体基因编码外显子的序列分析显示，外显子G第2881位存在单核苷酸替换，导致雄激素受体激素结合域第840位氨基酸处的精氨酸（CGT）转换为组氨酸（CAT）。家系研究表明，患者的母亲和外祖母是该突变的杂合携带者，而父亲不携带该突变，这支持了雄激素不敏感综合征是一种X染色体连锁疾病的观点。单个氨基酸替换可能解释了显示热稳定性的雄激素受体的定性异常，这被认为是患者不完全雄激素不敏感综合征的发病机制。
