Alternative splicing of the androgen receptor in polycystic ovary syndrome
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AbstractPolycystic 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.
All Author(s) ListWang FF, Pan JX, Liu Y, Meng Q, Lv PP, Qu F, Ding GL, Klausen C, Leung PCK, Chan HC, Yao WM, Zhou CY, Shi BW, Zhang JY, Sheng JZ, Huang HF
Journal nameProceedings of the National Academy of Sciences
Volume Number112
Issue Number15
Pages4743 - 4748
LanguagesEnglish-United Kingdom
KeywordsAR; folliculogenesis; hyperandrogenism; PCOS; splicing
Web of Science Subject CategoriesMultidisciplinary Sciences; Science & Technology - Other Topics

Last updated on 2021-08-12 at 00:20