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Novel PGK1 determines AR stability dependent on Spk2 and reprograms granular cell glucose metabolism to facilitate ovulation dysfunction

ABSTRACT: Ovulation disorder is the main characteristic of polycystic ovary syndrome (PCOS), but the concrete molecular mechanism is unclear. Phosphoglycerate kinase 1 (PGK1) plays an important role in the process of glycolytic cycles. Androgen and androgen receptor (AR) are considered as one of the critical factors in the prevalence of hyperandrogenemia and follicular development, and whether PGK1 participates in the metabolic reaction via AR in PCOS remains vague. PGK1 and AR proteins were highly expressed in PCOS luteinized granulosa cells and the PCOS-like mice ovary tissues. PGK1 increased lactate levels and deteriorated PCOS-like mouse metabolic disorder, and importantly, the phenotype of PCOS-like mice was rescued by PTX (paclitaxel) and the PGK1 and AR protein levels also decreased in the ovary. We demonstrated that PGK1 promoted AR translocation into the nuclear, and PGK1 was dependent on the E3 ligase Skp2 to repress the AR ubiquitination to improve the AR stability. In addition, we found that follicular development critical genes MAP2K6, KLF15, LRIG3 and MYOF were regulated by the PGK1-AR axis in the RNA-seq data, and axis also mediated cell proliferation and apoptosis. This study highlights the glycolysis key gene PGK1 to regulate metabolism in granular cell result in etiology of the PCOS. The PGK1-AR axis might provide a new therapy target of PCOS

ORGANISM(S): Homo sapiens

PROVIDER: GSE146856 | GEO | 2020/10/28

REPOSITORIES: GEO

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