title: Hypothalamic-pituitary-adrenocortical axis hypersensitivity and glucocorticoid receptor expression and function in women with polycystic ovary syndrome.
abstract: BACKGROUND
  Molecular mechanisms underlying pathophysiology of polycystic ovary syndrome (PCOS), especially those related to cortisol signaling, are poorly understood. We hypothesized that modulation of glucocorticoid receptor (GR) expression and function, may underlie possible PCOS-related impairment of feedback inhibition of hypothalamic-pituitary-adrenocortical (HPA) axis activity and thus contribute to increased adrenal androgen production in women with PCOS.
  
  
  METHODS
  24 normal-weight and 31 obese women with PCOS were compared to 25 normal-weight controls. Fasting blood samples were collected for measurements of serum concentrations of dehydroepiandrosterone sulfate, testosterone, sex hormone-binding globulin, insulin, basal cortisol and cortisol after oral administration of 0.5 mg dexamethasone. Concentrations of GR mRNA, GR protein, mineralocorticoid receptor (MR) protein and heat shock proteins (Hsps), as well as the number of GR per cell (B(max)) and its equilibrium dissociation constant (K(D)) were measured in isolated peripheral blood mononuclear cells.
  
  
  RESULTS
  An increase in HPA axis sensitivity to dexamethasone, an elevation of the GR protein concentration, and unaltered receptor functional status were found in both normal-weight and obese women with PCOS vs. healthy controls. Lymphocyte MR, Hsp90 and Hsp70 concentrations, and MR/GR ratio were similar in all groups. Correlation between B(max) and K(D) was weaker in the group of obese women with PCOS than in the other 2 groups.
  
  
  CONCLUSIONS
  The results did not confirm the initial hypothesis, but imply that PCOS is associated with increased GR protein concentration and HPA axis sensitivity to dexamethasone.
authors: Department of Biochemistry, Institute for Biological Research Siniša Stanković, University of Belgrade, Belgrade, Serbia. dvojnovic@ibiss.bg.ac.rs
authors: D Vojnović
authors: DV
authors: Milutinović
authors: D
authors: D
authors: Macut
authors: I
authors: I
authors: Božić
authors: J
authors: J
authors: Nestorov
authors: S
authors: S
authors: Damjanović
authors: G
authors: G
authors: Matić
mesh_terms: D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents; D015992:Body Mass Index; D025461:Feedback, Physiological / Q000187:drug effects; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology*; D007333:Insulin Resistance; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009765:Obesity / Q000150:complications; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D006728:Hormones; C497713:NR3C1 protein, human; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D012738:Sex Hormone-Binding Globulin