title: Hormonal therapy deregulates prostaglandin-endoperoxidase synthase 2 (PTGS2) expression in endometriotic tissues.
abstract: BACKGROUND
  Endometriosis is a common gynecologic condition characterized by an important inflammatory process mediated by the prostaglandin pathway. Oral contraceptives are the treatment of choice for symptomatic endometriotic women. However the effects of oral contraceptives use and prostaglandin pathway in endometriotic women are actually still unknown.
  
  
  OBJECTIVE
  To investigate the expression of prostaglandin pathway key genes in endometriotic tissue, affected or not by hormonal therapy, as compared with healthy endometrial tissue.
  
  
  METHODS
  This was a comparative laboratory study.
  
  
  METHODS
  This study was conducted in a tertiary-care university hospital.
  
  
  METHODS
  Seventy-six women, with (n = 46) and without (n = 30) histologically proven endometriosis.
  
  
  METHODS
  Prostaglandin-endoperoxidase synthase (PTGS)1, PTGS2, prostaglandin E receptor (PTGER)1, PTGER2, PTGER3, and PTGER4 mRNA levels in endometrium of disease-free women and in eutopic and ectopic endometrium of endometriosis-affected women. PTGS2 expression was further investigated by immunohistochemistry, using specific monoclonal antibodies. PTGS2 expression was analyzed at mRNA and protein levels and correlated with taking hormonal treatment.
  
  
  RESULTS
  PTGS2 expression was significantly increased in eutopic and ectopic endometrium as compared with healthy tissue (induction of 9.6- and 6.3-fold, respectively; P = .001). PTGS2 immunoreactivity increased gradually from normal endometrium to eutopic and ectopic endometrium (h-score of 96.7 ± 55.0, 128.3 ± 66.1, and 226.7 ± 62.6, respectively, P < .001). PTGER2, PTGER3, and PTGER4 expression increased significantly and gradually from normal to eutopic and ectopic endometrium, whereas PTGER1 remained unchanged. Patients under hormonal treatment had a higher PTGS2 expression at transcriptional and protein levels as compared with those without treatment (P = .002 and P = .025, respectively).
  
  
  CONCLUSIONS
  Prostaglandin pathway is strongly deregulated in eutopic and ectopic endometrium of women suffering from endometriosis for the benefit of an increased PTGS2 expression. We show for the first time that hormonal treatment appears to enhance even more PTGS2 expression. These results contribute to explain why medical treatment could fail to control endometriosis progression.
authors.affiliation: Université Paris Descartes (P.S., B.B., D.d.Z., C.C.), Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Universitaire Ouest, Centre Hospitalier Universitaire Cochin St Vincent de Paul, Department of Gynecology Obstetrics II and Reproductive Medicine, 75679 Paris, France; Université Paris Descartes (P.S., B.B., D.V., C.C.), Sorbonne Paris Cité, Inserm, Unité de Recherche U1016, Institut Cochin, Centre National de la Recherche Scientifique (Unité Mixte de Recherche 8104), 75014 Paris, France; Université Paris Descartes (P.S., F.B.), Sorbonne Paris Cité, Faculté de Médecine, Laboratoire d'Immunologie, Équipe d'Accueil 1833 Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, 75679 Paris Cedex 14, France; and Department of Gynecopathology (J-C.N., I.F., V.A.), Erasme University Hospital, Free University of Brussels, 1070 Brussels, Belgium.
authors.forename: Pietro
authors.initials: P
authors.lastname: Santulli
authors.forename: Bruno
authors.initials: B
authors.lastname: Borghese
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Noël
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fayt
authors.forename: Vincent
authors.initials: V
authors.lastname: Anaf
authors.forename: Dominique
authors.initials: D
authors.lastname: de Ziegler
authors.forename: Frederic
authors.initials: F
authors.lastname: Batteux
authors.forename: Daniel
authors.initials: D
authors.lastname: Vaiman
authors.forename: Charles
authors.initials: C
authors.lastname: Chapron
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage / Q000009:adverse effects*; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D004715:Endometriosis / Q000201:enzymology / Q000235:genetics*; D004717:Endometrium / Q000201:enzymology / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D011453:Prostaglandins / Q000378:metabolism; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000235:genetics / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000235:genetics / Q000378:metabolism; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000235:genetics / Q000378:metabolism; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000235:genetics / Q000378:metabolism
chemical_list: D003278:Contraceptives, Oral, Hormonal; C545635:PTGER1 protein, human; C545644:PTGER2 protein, human; C545647:PTGER3 protein, human; C545650:PTGER4 protein, human; D011453:Prostaglandins; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human