title: Insulin resistance directly contributes to androgenic potential within ovarian theca cells.
abstract: OBJECTIVE
  To investigate whether insulin resistance (IR) within theca cells may directly contribute to their hyperandrogenism, a heritable trait of polycystic ovary syndrome (PCOS).
  
  
  METHODS
  In vitro cell model.
  
  
  METHODS
  University-affiliated laboratory.
  
  
  METHODS
  Porcine ovaries.
  
  
  METHODS
  Ovarian theca cells from porcine follicles were isolated and cultured. Insulin resistance was induced in theca cells without (Con) or with dexamethasone (Dex); cells were further treated by troglitazone (Tro) and metformin (Met) in IR cells or by vehicle only in IR and Con cells.
  
  
  METHODS
  Medium glucose and T levels; reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot for insulin signal molecules and androgenic enzyme.
  
  
  RESULTS
  As compared with Con cells, Dex-treated cells had significantly lower [(3)H]-glucose uptake (565 +/- 58 cpm/10(6) vs. 1077 +/- 78 cpm/10(6)) but higher medium glucose levels (16.31 +/- 0.39 nmol/L vs. 10.62 +/- 1.02 nmol/L) and had approximately twofold T levels (0.82 +/- 0.20 microg/L vs. 0.38+/-0.08 microg/L). Troglitazone and Met significantly reduced the medium glucose and testosterone concentrations to levels comparable to those in Con cells. The RT-PCR and Western blot showed that the two sensitizers in different ways reversed the altered messenger RNA and protein expression of insulin receptor substrate-1, glucose transporter-4, peroxisome proliferator-activated receptor-gamma, and 17 alpha-hydroxylase in Dex-induced IR cells.
  
  
  CONCLUSIONS
  Insulin resistance induced by Dex could directly exaggerate androgenic potential within theca cells, suggesting the possible involvement of this ovarian metabolic phenotype in PCOS hyperandrogenism.
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.
authors.forename: JunWei
authors.initials: J
authors.lastname: Qu
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Wu
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.forename: Lihui
authors.initials: L
authors.lastname: Hou
authors.forename: Risto
authors.initials: R
authors.lastname: Erkkola
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002839:Chromans / Q000494:pharmacology*; D005260:Female; D051275:Glucose Transporter Type 4 / Q000187:drug effects / Q000235:genetics*; D055504:Insulin Receptor Substrate Proteins / Q000187:drug effects / Q000235:genetics; D007333:Insulin Resistance / Q000502:physiology*; D008687:Metformin / Q000494:pharmacology*; D047495:PPAR gamma / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013254:Steroid 17-alpha-Hydroxylase / Q000187:drug effects / Q000235:genetics; D013552:Swine; D013799:Theca Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
chemical_list: D000728:Androgens; D002839:Chromans; D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D008687:Metformin; D013254:Steroid 17-alpha-Hydroxylase; D000077288:Troglitazone