title: Endometriosis expresses a molecular pattern consistent with decreased retinoid uptake, metabolism and action.
abstract: BACKGROUND
  Retinoic acid (RA) regulates key biological processes, including differentiation, apoptosis and cell survival. RA mediates induction of 17 beta-hydroxysteroid dehydrogenase type 2 mRNA, catalyzing the conversion of estradiol to estrone, in endometrium but not endometriosis because of a defect in endometriotic stromal cells. This defect may involve both the uptake and metabolism of RA. In this study, we analyze the expression of genes involved in RA signaling in normal endometrium and endometriosis.
  
  
  METHODS
  Tissue and stromal cells from ovarian endometriomas and eutopic endometrium from disease-free women were collected. Real-time reverse transcription-polymerase chain reaction was used to measure mRNA levels. Western blotting was used to evaluate protein expression.
  
  
  RESULTS
  We found that endometriotic tissue and stromal cells demonstrated significantly decreased mRNA expression of the major genes involved in RA signaling, including STRA6, CRBP1, ALDH1A2, CRABP2 and FABP5. We found increased levels of CYP26B1, responsible for RA metabolism. Nuclear extracts showed that RARα, RXRα and PPARβ/δ were underexpressed in both tissues and stromal cells from endometriotic tissue. Differences in protein levels were confirmed by western blotting.
  
  
  CONCLUSIONS
  Endometriosis is characterized by a gene expression pattern suggesting a decrease in uptake and metabolism of RA. Because RA is integral in regulating key biological processes involved in cell survival, this alteration could partially explain the resistance to apoptosis found in endometriosis.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Reproductive Biology, Feinberg School of Medicine at Northwestern University, 303 Superior Street, Suite 4-123, Chicago, IL 60611, USA. mpavone@nmff.org
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Pavone
authors.forename: Matthew
authors.initials: M
authors.lastname: Dyson
authors.forename: Scott
authors.initials: S
authors.lastname: Reirstad
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pearson
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishikawa
authors.forename: You Hong
authors.initials: YH
authors.lastname: Cheng
authors.forename: Serdar E
authors.initials: SE
authors.lastname: Bulun
mesh_terms: D000328:Adult; D000080924:Aldehyde Dehydrogenase 1 Family; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis; D050697:Retinal Dehydrogenase / Q000096:biosynthesis*; D000072516:Retinoic Acid 4-Hydroxylase; D054840:Retinol-Binding Proteins, Cellular / Q000096:biosynthesis*; D017154:Stromal Cells / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*; D014801:Vitamin A / Q000378:metabolism
chemical_list: C493412:FABP5 protein, human; D050556:Fatty Acid-Binding Proteins; D008565:Membrane Proteins; D018168:Receptors, Retinoic Acid; D054840:Retinol-Binding Proteins, Cellular; C519685:STRA6 protein, human; C082928:retinoic acid binding protein II, cellular; D014801:Vitamin A; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; C000607079:CYP26B1 protein, human; D000072516:Retinoic Acid 4-Hydroxylase; D000080924:Aldehyde Dehydrogenase 1 Family; C545372:ALDH1A2 protein, human; D050697:Retinal Dehydrogenase