title: Activated glucocorticoid and eicosanoid pathways in endometriosis.
abstract: OBJECTIVE
  To define altered gene expression networks in endometriosis.
  
  
  METHODS
  Experiments using endometriotic tissues and primary cells.
  
  
  METHODS
  Division of Reproductive Biology Research, Northwestern University.
  
  
  METHODS
  Premenopausal women.
  
  
  METHODS
  Matched samples of eutopic endometrium and ovarian endometriosis (n = 8 patients) were analyzed by microarray and verified in a separate set of tissues (n = 6 patients). Experiments to define signaling pathways were performed in primary endometriotic stromal cells (n = 12 patients).
  
  
  METHODS
  Using a genome-wide in vivo approach, we identified 1,366 differentially expressed genes and a new gene network favoring increased glucocorticoid levels and action in endometriosis.
  
  
  RESULTS
  Transcript and protein levels of 11β-hydroxysteroid dehydrogenase (HSD11B1), which produces cortisol, the biologically active glucocorticoid, were strikingly higher, whereas messenger RNA (mRNA) levels of the cortisol-degrading HSD11B2 enzyme were significantly lower in endometriotic tissue. Glucocorticoid receptor mRNA and protein levels were significantly higher in endometriosis. The inflammatory cytokine tumor necrosis factor robustly induced mRNA and protein levels of HSD11B1 and glucocorticoid receptor but suppressed HSD11B2 mRNA in primary endometriotic stromal cells, suggesting that tumor necrosis factor stimulates cortisol production and action. We also uncovered a subset of genes critical for prostaglandin synthesis and degradation, which favor high eicosanoid levels and activity in endometriosis.
  
  
  CONCLUSIONS
  The proinflammatory milieu of the endometriotic lesion stimulates cortisol synthesis and action in endometriotic lesions.
authors.affiliation: Division of Reproductive Biology Research, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Monsivais
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Bray
authors.forename: Emily
authors.initials: E
authors.lastname: Su
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Pavone
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Dyson
authors.forename: Antonia
authors.initials: A
authors.lastname: Navarro
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kakinuma
authors.forename: Serdar E
authors.initials: SE
authors.lastname: Bulun
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D015777:Eicosanoids / Q000378:metabolism*; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D046228:Microarray Analysis; D008875:Middle Aged; D010049:Ovarian Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult
chemical_list: D015777:Eicosanoids; D005938:Glucocorticoids