Sultan Ch, Gobinet J, Terouanne B, Paris F, Belon Ch, Jalaguier S, Georget V, Poujol N, Auzou G, Lumbroso S
Unité d'Endocrinologie-Gynécologie Pédiatriques, Service de Pédiatrie I, Hôpital Anaud de Villeneuve, Service d'Hormonologie (Développement et Reproduction), CHU Montpellier.
J Soc Biol. 2002;196(3):223-40.
Androgens play a crucial role in the development, maintenance and regulation of male phenotype and reproductive physiology through the androgen receptor, a transcription factor. Testosterone or dihydrotestosterone binding induces a trans-conformation of the androgen receptor and allows its translocation into the nucleus, where it recognizes specific DNA sequences. Recent developments in molecular genetics, as well as structural analysis of the androgen receptor, allow a better understanding of the structure/function relationship of this nuclear receptor. Molecular analyses of androgen insensitivity syndrome, as well as hormone-resistant prostate cancer, Kennedy's disease and isolated male infertility, have been proved useful as privileged models for this purpose. In the absence of identified AR receptor mutations in androgen insensitivity syndromes, abnormalities of transcriptional cofactor should be considered. Finally, identification of androgen-dependent genes will be helpful for evaluating the degree of the molecular defect of androgen action within target cells.
雄激素通过雄激素受体(一种转录因子)在男性表型和生殖生理学的发育、维持及调节中发挥关键作用。睾酮或双氢睾酮结合会诱导雄激素受体发生反式构象变化,并使其易位至细胞核,在细胞核中它可识别特定的DNA序列。分子遗传学的最新进展以及雄激素受体的结构分析,有助于更好地理解这种核受体的结构/功能关系。雄激素不敏感综合征、激素抵抗性前列腺癌、肯尼迪病及特发性男性不育症的分子分析,已被证明是用于此目的的重要模型。在雄激素不敏感综合征中,若未发现雄激素受体基因突变,则应考虑转录辅因子异常。最后,鉴定雄激素依赖性基因将有助于评估靶细胞内雄激素作用的分子缺陷程度。