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https://hdl.handle.net/2440/113951
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Type: | Journal article |
Title: | Alternative splicing of the androgen receptor in polycystic ovary syndrome |
Author: | Wang, F. Pan, J. Liu, Y. Meng, Q. Lv, P. Qu, F. Ding, G.-L. Klausen, C. Leung, P.C.K. Chan, H.C. Yao, W. Zhou, C.-Y. Shi, B. Zhang, J. Sheng, J. Huang, H. |
Citation: | Proceedings of the National Academy of Sciences of USA, 2015; 112(15):4743-4748 |
Publisher: | National Academy of Sciences |
Issue Date: | 2015 |
ISSN: | 0027-8424 1091-6490 |
Statement of Responsibility: | Fangfang Wang, Jiexue Pan, Ye Liu, Qing Meng, Pingping Lv, Fan Qu, Guo-Lian Ding, Christian Klausen, Peter C. K. Leung, Hsiao Chang Chan, Weimiao Yao, Cai-Yun Zhou, Biwei Shi, Junyu Zhang, Jianzhong Sheng and Hefeng Huang |
Abstract: | 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. |
Keywords: | AR; splicing; hyperandrogenism; folliculogenesis; PCOS |
Rights: | The author(s) retains copyright to individual PNAS articles, and the National Academy of Sciences of the United States of America (NAS) holds copyright to the collective work and retains an exclusive License to Publish these articles, except for open access articles submitted beginning September 2017. For such open access articles, NAS retains a nonexclusive License to Publish, and these articles are distributed under a CC BY-NC-ND license. For volumes 106–114 (2009–September 2017), the author(s) retains copyright to individual articles, and NAS retains an exclusive License to Publish these articles and holds copyright to the collective work. |
DOI: | 10.1073/pnas.1418216112 |
Published version: | http://dx.doi.org/10.1073/pnas.1418216112 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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hdl_113951.pdf | Published version | 1.56 MB | Adobe PDF | View/Open |
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