雄激素受体基因突变受试者的临床和生化调查及分子分析。
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魏德曼W, Linck B, Haupt H, Mentrup B, Romalo G, Stockklauser K, Brinkmann AO, Schweikert HU, Spindler KD
雄激素受体基因突变受试者的临床和生化调查及分子分析。
中国性(Oxf)。1996年12月,45(6):733 - 9。
- PubMed ID
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9039340 (在PubMed］
- 摘要
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目的:46、XY核型、血液中雄激素水平正常甚至升高的受试者雄激素不敏感综合征(AIS)的特征是男性分化和雄激素化的各种畸变。AIS常伴有广谱异常的雄激素受体(AR)结合特征。为了研究雄性化缺陷程度与雄激素结合异常类型和/或AR基因突变性质之间的相关性，我们在临床和生化特征良好且具有不同程度雄激素抵抗的患者中测定了AR蛋白的雄激素结合特征和AR基因序列。设计与患者:在20例不同程度男性化缺陷(2例CAIS，完全AIS;PAIS 18例，部分AIS患者)。采用PCR-SSCP方法对20例患者的AR基因进行分析。如果电泳迁移率异常，则对相应的外显子进行测序。结果:2例CAIS患者和7例PAIS患者AR基因发生突变。其中两个突变发生在DNA结合区域，其他所有突变都发生在配体结合区域。在11例严重雄性化缺陷患者中，PCR-SSCP未检测到异常行为。 Transcriptional activation studies of two mutant ARs revealed that an approximately tenfold higher androgen concentration (methyltrienolone) is necessary to achieve maximal response as compared to the wild type AR. CONCLUSIONS: There is no obvious relation between the degree of androgen resistance and the binding parameters of the AR and/or the nature of mutation in the AR gene. Androgen insensitivity syndrome can occur despite normal androgen binding and presumably non-mutated AR genes. Even if there is abnormal binding of androgen and/or a mutation in the AR gene there is no clear-cut relationship between these parameters and the degree of virilization defects. Thus, in a proportion of patients, neither the determination of binding parameters of the AR nor the detection of mutations in the AR gene are sufficient to understand the mechanisms underlying the androgen insensitivity syndrome.