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MOLECULAR ANALYSIS FOR HUMAN ANDROGEN RECEPTOR GENE IN CASES WITH ANDROGEN INSENSITIVITY SYNDROME

雄激素不敏感综合征患者雄激素受体基因的分子分析

基本信息

批准号：
04671401
负责人：
KOMORI Shinji
金额：
$ 1.34万
依托单位：
HYOGO COLLEGE OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04671401/
关键词：
Androgen receptor gene Androgen insensitivity syndrome point mutation 遺伝子解析 PCR

项目摘要

Complete androgen insensitivity syndrome is caused by X chromosome linked disorder resulting in a target organ insensitivity to androgen. Two kinds of variants have been described in this syndrome. In the first variant, the binding of [3H] dihydrotestosterone(17beta-hydroxy-5alpha-androstan-3-one) to the androgen receptor is undetectable (receptor-negative), whereas in the second variant normal levels of androgen receptor are detectable but the binding of [3H] dihydrotestosterone to the androgen receptor is significantly thermolabile under a certain condition (receptor-positive). In receptor-negative cases, genetic disorders of androgen receptor gene have been demonstrated. On the other hand, the genetic disorder of androgen receptor in receptor-positive cases is little known. In this study, the gene structure of androgen receptor in a receptor-positive case using polymerase chain reaction technique is studied in th fibroblasts cultured from genital skin. The result demonstrated that the substitution of a nucleotide (guanine - cytosine) in exon G of the androgen receptor caused the replacement of an amino acid in position 820 (glycine - alanine) which occurred in the hormone binding domain of the androgen receptor. The substitution of th nucleotide might explain for thermolability of the androgen receptor in a case with receptor-positive androgen insensitivity syndrome.

完全雄激素不敏感综合征是由X染色体相关疾病导致靶器官对雄激素不敏感引起的。在这种综合征中已经描述了两种变体。在第一种变异中，[3H]双氢睾酮（17β -羟基-5 α -雄激素-3- 1）与雄激素受体的结合无法检测到（受体阴性），而在第二种变异中，可以检测到正常水平的雄激素受体，但[3H]双氢睾酮与雄激素受体的结合在一定条件下（受体阳性）具有显著的热稳定性。在受体阴性的情况下，雄激素受体基因的遗传障碍已被证实。另一方面，受体阳性病例中雄激素受体的遗传障碍知之甚少。本研究利用聚合酶链反应技术，在培养的生殖皮肤成纤维细胞中研究了受体阳性病例中雄激素受体的基因结构。结果表明，雄激素受体外显子G上一个核苷酸（鸟嘌呤-胞嘧啶）的替换导致雄激素受体激素结合域820位氨基酸（甘氨酸-丙氨酸）的替换。在受体阳性雄激素不敏感综合征的情况下，核苷酸的取代可能解释雄激素受体的耐热性。