Transcription of androgen receptor and 5α-reductase II in genital fibroblasts from patients with androgen insensitivity syndrome
Transcription of androgen receptor and 5α-reductase II in genital fibroblasts from patients with androgen insensitivity syndrome
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DOI：
10.1016/s0960-0760(00)00174-6
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发表时间：
2000-12-31
影响因子：
4.1
通讯作者：
Hiort, O
中科院分区：
文献类型：
--
作者：
Hellwinkel, OJC;Bassler, J;Hiort, O
雄激素不敏感综合征(AIS)患者在胚胎发育和青春期停滞期间男性化功能受损通常是由雄激素受体(AR)或5α还原酶II(5RII)基因突变引起的。然而，相同的突变可能会导致显著不同的表型。为了研究这是否可能是由患者生殖器区域(GF)成纤维细胞的转录速率个别改变引起的，我们应用了针对AR-和5RII-转录本的竞争性逆转录聚合酶链式反应(竞争RT-PCR)。我们可以证明，部分和完全AIS患者以及AR-或5RII-基因错义突变的患者细胞中AR-和5RII-mRNA的浓度与同龄正常对照组相比是正常的或仅适度降低。然而，在一名携带AR基因过早停止密码子的患者中，检测到AR转录水平显著降低。我们的结论是，在因错义突变而导致的不完全男性化障碍患者中，AR和5RII的转录调节通常遵循正常模式。相应地，过早停止密码子。因此，在雄激素不敏感综合征中，成纤维细胞中AR和5RII转录速率的改变似乎不是雄激素不敏感综合征中不同的基因-表型相关性的原因。(C)2001爱思唯尔科学有限公司。保留所有权利。
Impaired virilisation during embryonic development and pubertal arrest in patients with androgen insensitivity syndrome (AIS) is usually caused by mutations in the androgen receptor (AR)- or the 5 alpha -reductase II (5RII) gene. However identical mutations may lead to strikingly different phenotypes. To investigate whether this may be caused by individually altered transcription rates in fibroblasts fron the genital region (GF) from affected patients, we applied competitive reverse transcribed PCRs (competitive RT-PCR) targeting AR- and 5RII-transcripts. We could demonstrate that AR- and 5RII-mRNA concentrations in cells from patients with partial and complete AIS adn missense mutations in the AR- or 5RII-gene are normal or only moderately lowered compared to equally aged normal controls. However, in a patient bearing a premature stop-eodon in the AR-gene a considerably lowered AR-transcript level was detected. We conclude, that in patients with incomplete virilisation disorders due to missense mutations, transcription regulation of AR and 5RII generally follows normal patterns. Accordingly, the premature stop-condon. Therefore, altered AR- and 5RII-transcription rates in fibroblasts from the GF do not seem to be the cause for the variable genotype-phenotype correlation in androgen insensitivity syndrome. (C) 2001 Elsevier Science Ltd. All rights reserved.