Alternative splicing of the androgen receptor in polycystic ovary syndrome
Alternative splicing of the androgen receptor in polycystic ovary syndrome
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多囊卵巢综合征中雄激素受体的选择性剪接。
DOI：
10.1073/pnas.1418216112
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发表时间：
2015-04-14
影响因子：
11.1
通讯作者：
Huang, Hefeng
中科院分区：
文献类型：
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作者：
Wang, Fangfang;Pan, Jiexue;Huang, Hefeng
多囊卵巢综合征（PCOS）是女性最常见的内分泌疾病之一，也是女性生育能力低下的主要原因。PCOS的病理生理机制仍有待阐明。在这里，我们确定了雄激素受体（AR）的两种选择性剪接变体（ASV），插入和缺失亚型，在颗粒细胞（GC）中，与62%的PCOS患者相似。AR ASV与显著的高雄激素血症和卵泡发育异常密切相关，并且在所有无PCOS的对照受试者中均不存在。选择性剪接显著改变人类GC中全基因组AR募集和雄激素诱导的雄激素代谢和卵泡发生相关基因的表达这些研究结果建立了选择性剪接的AR在GC的高雄激素血症和异常卵泡发生在PCOS的主要致病机制。
Polycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders and a leading cause of female subfertility. The mechanism underlying the pathophysiology of PCOS remains to be illustrated. Here, we identify two alternative splice variants (ASVs) of the androgen receptor (AR), insertion and deletion isoforms, in granulosa cells (GCs) in similar to 62% of patients with PCOS. AR ASVs are strongly associated with remarkable hyperandrogenism and abnormalities in folliculogenesis, and are absent from all control subjects without PCOS. Alternative splicing dramatically alters genome-wide AR recruitment and androgeninduced expression of genes related to androgen metabolism and folliculogenesis in human GCs. These findings establish alternative splicing of AR in GCs as the major pathogenic mechanism for hyperandrogenism and abnormal folliculogenesis in PCOS.