Brown T R, Scherer P A, Chang Y T, Migeon C J, Ghirri P, Murono K, Zhou Z
Department of Population Dynamics, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205.
Eur J Pediatr. 1993;152 Suppl 2:S62-9. doi: 10.1007/BF02125442.
Androgen insensitivity syndromes represent one cause of human male pseudohermaphroditism related to defects in the androgen receptor. The formation of a biologically active androgen receptor complex with testosterone and 5 alpha-dihydrotestosterone is required for normal androgen action during fetal development and differentiation of the internal accessory sex glands and external genitalia. Cloning of the human androgen receptor complementary DNA and genetic screening of human subjects with the clinical and biochemical features of androgen insensitivity using the polymerase chain reaction, denaturing gradient gel electrophoresis and nucleotide sequencing techniques have led to the identification of molecular defects in the androgen receptor. The complexity of phenotypic presentation by affected subjects with the complete or partial forms of androgen insensitivity is represented by the heterogeneity of androgen receptor gene mutations which include deletions and point mutations, with the latter causing inappropriate splicing of RNA, premature termination of transcription and amino acid substitutions. The naturally occurring mutations in the androgen receptor of subjects with androgen insensitivity represent a base upon which we can increase our understanding of the structure and function of the androgen receptor in normal physiology and disease.
雄激素不敏感综合征是人类男性假两性畸形的一个病因，与雄激素受体缺陷有关。在胎儿发育以及内附属性腺和外生殖器分化过程中，正常的雄激素作用需要形成具有生物学活性的雄激素受体复合物，该复合物由睾酮和5α-二氢睾酮组成。通过聚合酶链反应、变性梯度凝胶电泳和核苷酸测序技术，对具有雄激素不敏感临床和生化特征的人类受试者进行人类雄激素受体互补DNA克隆和基因筛查，已鉴定出雄激素受体的分子缺陷。完全或部分形式的雄激素不敏感患者所表现出的表型复杂性，体现在雄激素受体基因突变的异质性上，这些突变包括缺失和点突变，后者会导致RNA剪接异常、转录提前终止和氨基酸替代。雄激素不敏感患者雄激素受体的自然发生突变，为我们增进对正常生理学和疾病中雄激素受体结构与功能的理解奠定了基础。
