Proceedings of the National Academy of Sciences of the United States of America · 2015
Alternative splicing of the androgen receptor in polycystic ovary syndrome.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Wang Fangfang, Pan Jiexue, Liu Ye, Meng Qing, Lv Pingping, Qu Fan, Ding Guo-Lian, Klausen Christian, Leung Peter C K, Chan Hsiao Chang, Yao Weimiao, Zhou Cai-Yun, Shi Biwei, Zhang Junyu, Sheng Jianzhong, Huang Hefeng
Аннотация
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 ∼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 androgen-induced 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.
Предметные рубрики MeSH
AdultAlternative SplicingBase SequenceCells, CulturedDehydroepiandrosteroneFemaleGene Expression ProfilingGenome-Wide Association StudyGranulosa CellsHEK293 CellsHumansHyperandrogenismINDEL MutationOogenesisOvarian FolliclePolycystic Ovary SyndromeProtein IsoformsReceptors, AndrogenReverse Transcriptase Polymerase Chain ReactionTestosterone