title: Abundance and Localization of Progesterone Receptor Isoforms in Endometrium in Women With and Without Endometriosis and in Peritoneal and Ovarian Endometriotic Implants.
abstract: BACKGROUND
  Several studies suggest that resistance to progesterone may contribute to the pathophysiology of endometriosis. Progesterone mediates its biological activity via the 2 progesterone receptor (PR) isoforms (PR-A and PR-B). Effects of progesterone are determined by the PR-A:PR-B ratio such that a PR-B-dominant state promotes progesterone signaling, whereas a PR-A-dominant state decreases progesterone responsiveness. Our objective was to compare the abundance and cellular localization of the PR isoforms in endometrium and endometriotic lesions from women with and without peritoneal and ovarian endometriosis.
  
  
  METHODS
  This in vitro study was conducted in a tertiary care facility. Reproductive-age women with surgically diagnosed endometriosis (n = 18) and asymptomatic control individuals (n = 20) were prospectively recruited at the late proliferative and the early secretory phases. At laparoscopy, samples of eutopic endometrium, peritoneal and ovarian endometriosis, and disease-free peritoneum were obtained for subsequent immunohistochemical and immunoblot analysis of PR-B and total PR localization and PR-A and PR-B abundance, respectively.
  
  
  RESULTS
  The PR-A and PR-B were detected in eutopic endometrium and in peritoneal and ovarian endometriosis but not in disease-free peritoneum from patients with and without endometriosis. In peritoneal endometriosis, PR-A was the predominant isoform detected, whereas both receptors were detected in ovarian endometriosis and eutopic endometrium. In eutopic endometrium, levels of PR-A were significantly elevated in women with endometriosis compared with women without disease, regardless of menstrual phase. The PR-A levels were significantly elevated in ovarian endometriosis compared with peritoneal endometriosis.
  
  
  CONCLUSIONS
  Endometriotic lesions and eutopic endometrium from women with endometriosis are uniform in a PR-A-dominant state. The data suggest that menstrual efflux of a PR-A-dominant endometrial tissue into the peritoneal cavity may play a role in the pathophysiology of endometriosis.
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University, Cleveland, OH, USA Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Cleveland, OH, USA Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, The University of British Columbia, Vancouver, Canada bedaiwymmm@yahoo.com.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Bedaiwy
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University, Cleveland, OH, USA Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: Wissam
authors.initials: W
authors.lastname: Dahoud
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University, Cleveland, OH, USA Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: Yelena
authors.initials: Y
authors.lastname: Skomorovska-Prokvolit
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University, Cleveland, OH, USA Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yi
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University, Cleveland, OH, USA Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Liu
authors.affiliation: Department of OB/GYN and Women's Health Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Falcone
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University, Cleveland, OH, USA Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Hurd
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University, Cleveland, OH, USA Department of Obstetrics and Gynecology, University Hospitals Case Medical Center, Cleveland, OH, USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Mesiano
mesh_terms: D000328:Adult; D001706:Biopsy; D015153:Blotting, Western; D016022:Case-Control Studies; D049109:Cell Proliferation; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D004717:Endometrium / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D010535:Laparoscopy; D010053:Ovary / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D010537:Peritoneum / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D011446:Prospective Studies; D020033:Protein Isoforms; D011980:Receptors, Progesterone / Q000032:analysis*
chemical_list: D020033:Protein Isoforms; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B
keywords: endometriosis; endometrium; progesterone receptors