title: SET/PP2A system regulates androgen production in ovarian follicles in vitro.
abstract: SET has multiple cell functions including nucleosome assembly, histone binding, transcription control, and cell apoptosis. In ovaries SET is predominantly expressed in theca cells and oocytes. In our study, SET overexpression in theca cells stimulated testosterone production whereas SET knockdown decreased testosterone production. Moreover, SET negatively regulated PP2A activity. Treatment with PP2A inhibitor okadaic acid (OA) led to increased testosterone synthesis, while treatment with PP2A activators resulted in the decreased testosterone synthesis. Furthermore, PP2A knockdown confirmed the key role of PP2A in the testosterone synthesis, and OA was able to block the AdH1-SiRNA/SET-mediated inhibition of testosterone production. The central role of PP2A in SET-mediated regulation of testosterone production was confirmed by the finding that SET promoted the lyase activity of P450c17 and that PP2A inhibited its lyase activity. Taken together, these results reveal a specific, SET-initiated, PP2A-mediated, pathway that leads to the increased lyase activity of P450c17 and testosterone biosynthesis.
authors.affiliation: The State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. gaolingling86@gmail.com
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Gao
authors.forename: Xiao-Qiang
authors.initials: XQ
authors.lastname: Liu
authors.forename: Bo-Qun
authors.initials: BQ
authors.lastname: Xu
authors.forename: Shi-Wen
authors.initials: SW
authors.lastname: Jiang
authors.forename: Yu-Gui
authors.initials: YG
authors.lastname: Cui
authors.forename: Jia-Yin
authors.initials: JY
authors.lastname: Liu
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D056488:Histone Chaperones; D051379:Mice; D008813:Mice, Inbred ICR; D019319:Okadaic Acid / Q000494:pharmacology; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis*; D013799:Theca Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D056488:Histone Chaperones; D015513:Oncogene Proteins; D034741:RNA, Small Interfering; C557500:SET protein, mouse; D019319:Okadaic Acid; D013739:Testosterone; D013254:Steroid 17-alpha-Hydroxylase; D054648:Protein Phosphatase 2