title: Local Regeneration of Cortisol by 11β-HSD1 Contributes to Insulin Resistance of the Granulosa Cells in PCOS.
abstract: Insulin resistance (IR) of the granulosa cells may account for the ovarian dysfunctions observed in polycystic ovarian syndrome (PCOS). The underlying mechanism remains largely unresolved.
  
  
  
  The objective of the study was to investigate the relationship of IR of the granulosa cells with cortisol in the follicular fluid and 11β-hydroxysteroid dehydrogenase 1 and 2 (11β-HSD1 and -2) in the granulosa cells in PCOS.
  
  
  
  Follicular fluid and granulosa cells were collected from non-PCOS and PCOS patients with and without IR to measure cortisol concentration and the amounts of 11β-HSD1 and -2, which were then correlated with IR status. The effects of cortisol on the expression of genes pertinent to IR were studied in cultured human granulosa cells.
  
  
  
  Cortisol concentration in the follicular fluid, 11β-HSD1 but not 11β-HSD2 mRNA in the granulosa cells were significantly elevated in PCOS with IR. Increased reductase and decreased oxidase activities of 11β-HSD were observed in granulosa cells in PCOS with IR. In cultured granulosa cells, insulin-induced Akt phosphorylation was significantly attenuated by cortisol. Cortisol not only increased phosphatase and tensin homolog deleted on chromosome 10, an inhibitor of Akt phosphorylation, but also 11β-HSD1 in the cells.
  
  
  
  Increased 11β-HSD1 expression and its reductase activity in granulosa cells are the major causes of increased cortisol concentration in the follicular fluid of PCOS with IR. The consequent excessive cortisol might contribute to IR of the granulosa cells in PCOS patients by attenuating Akt phosphorylation via induction of phosphatase and tensin homolog deleted on chromosome 10 expression, which might be further exacerbated by the induction of 11β-HSD1.
authors.affiliation: Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, and Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, People's Republic of China.
authors.forename: Qinling
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, and Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, People's Republic of China.
authors.forename: Rujuan
authors.initials: R
authors.lastname: Zuo
authors.affiliation: Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, and Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, People's Republic of China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: He
authors.affiliation: Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, and Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, and Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, People's Republic of China.
authors.forename: Zi-Jiang
authors.initials: ZJ
authors.lastname: Chen
authors.affiliation: Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, and Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, and Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, People's Republic of China.
authors.forename: Kang
authors.initials: K
authors.lastname: Sun
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism; D000328:Adult; D005260:Female; D015571:Follicular Fluid / Q000378:metabolism; D006107:Granulosa Cells / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D010766:Phosphorylation; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D055815:Young Adult
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D051057:Proto-Oncogene Proteins c-akt; D006854:Hydrocortisone