title: Expression and activity of Rac1 is negatively affected in the dehydroepiandrosterone induced polycystic ovary of mouse.
abstract: BACKGROUND
  Polycystic ovarian syndrome (PCOS) is characterized by the presence of multiple follicular cysts, giving rise to infertility due to anovulation. This syndrome affects about 10% of women, worldwide. The exact molecular mechanism leading to PCOS remains obscure. RhoGTPase has been associated with oogenesis, but its role in PCOS remains unexplored. Therefore, we attempted to elucidate the Vav-Rac1 signaling in PCOS mice model.
  
  
  METHODS
  We generated a PCOS mice model by injecting dehydroepiandrosterone (DHEA) for a period of 20 days. The expression levels of Rac1, pRac1, Vav, pVav and Caveolin1 were analyzed by employing immuno-blotting and densitometry. The association between Vav and Rac1 proteins were studied by immuno-precipitation. Furthermore, we analyzed the activity of Rac1 and levels of inhibin B and 17β-estradiol in ovary using biochemical assays.
  
  
  RESULTS
  The presence of multiple follicular cysts in ovary were confirmed by histology. The activity of Rac1 (GTP bound state) was significantly reduced in the PCOS ovary. Similarly, the expression levels of Rac1 and its phosphorylated form (pRac1) were decreased in PCOS in comparison to the sham ovary. The expression level and activity (phosphorylated form) of guanine nucleotide exchanger of Rac1, Vav, was moderately down-regulated. We observed comparatively increased expressions of Caveolin1, 17β-estradiol, and inhibin B in the polycystic ovary.
  
  
  CONCLUSIONS
  We conclude that hyperandrogenization (PCOS) by DHEA diminishes ovarian Rac1 and Vav expression and activity along with an increase in expression of Caveolin1. This is accompanied by an increase in the intra-ovarian level of '17 β-estradiol and inhibin B.
authors.forename: Vineet Kumar
authors.initials: VK
authors.lastname: Maurya
authors.forename: Chadchan
authors.initials: C
authors.lastname: Sangappa
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.forename: Sahil
authors.initials: S
authors.lastname: Mahfooz
authors.forename: Archana
authors.initials: A
authors.lastname: Singh
authors.forename: Singh
authors.initials: S
authors.lastname: Rajender
authors.affiliation: Division of Endocrinology, Life Science North 111B/101, CSIR-Central Drug Research Institute, B,S, 10/1, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. rajesh_jha@cdri.res.in.
authors.forename: Rajesh Kumar
authors.initials: RK
authors.lastname: Jha
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism; D003687:Dehydroepiandrosterone; D004195:Disease Models, Animal; D015536:Down-Regulation; D004958:Estradiol / Q000378:metabolism; D005260:Female; D007265:Inhibins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010053:Ovary / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: C495541:Cav1 protein, mouse; D051242:Caveolin 1; D051567:Proto-Oncogene Proteins c-vav; C107953:RAC1 protein, human; C422364:inhibin B; D003687:Dehydroepiandrosterone; D004958:Estradiol; D007265:Inhibins; D020830:rac1 GTP-Binding Protein