title: Inhibition of steroid sulfatase decreases endometriosis in an in vivo murine model.
abstract: BACKGROUND
  Steroid sulfatase (STS) is involved in estrogen biosynthesis and expressed in eutopic and ectopic endometrium of disease-free and endometriosis patients. The present study was designed to investigate its role in endometriosis development.
  
  
  METHODS
  Human endometrial explants were cultured on inserts for 24 h to assess the effectiveness of an STS inhibitor (STS-I), estradiol-3-O-sulfamate (E2MATE), on STS activity in endometrial tissue. Endometriosis was induced in mice, and E2MATE (or vehicle alone) was given orally for 21 days. Plasma estradiol levels were measured, and STS activity was assessed in murine organs (uterus, liver and leukocytes) and in lesions. Lesion number, weight and size (morphometry) were quantified. Lesion STS and progesterone receptor (PR) expression, proliferation and apoptosis rates were determined by immunohistochemistry.
  
  
  RESULTS
  In vitro, addition of 1 µM E2MATE to the culture medium resulted in decreased STS activity in endometrial explants (P < 0.001). Treatment of mice with E2MATE (1.0 and 0.5 mg/kg) did not modify plasma estradiol levels, but inhibited STS activity in murine uterus (P < 0.05), liver (P < 0.001) and leukocytes (P < 0.001), as well as in induced lesions (P < 0.05). E2MATE reduced lesion weight (P < 0.01) and size (P < 0.05), but had no impact on proliferation or apoptosis rates, nor STS protein expression. Stromal edema was observed in the uterus of animals treated with E2MATE, but not in the stroma of lesions. Increased PR expression was detected in endometriotic lesions (P < 0.001).
  
  
  CONCLUSIONS
  E2MATE was shown to effectively inhibit STS activity in endometrial tissue in vitro. In vivo, E2MATE decreased endometriosis development without affecting systemic estradiol levels. Use of STS-I could therefore be of potential interest in endometriosis treatment.
authors: Université Catholique de Louvain, Institut de Recherche Expérimentale et Clinique, Department of Gynecology, Cliniques Universitaires St Luc, Avenue Hippocrate 10, 1200 Brussels, Belgium.
authors: S
authors: S
authors: Colette
authors: S
authors: S
authors: Defrère
authors: J C
authors: JC
authors: Lousse
authors: A
authors: A
authors: Van Langendonckt
authors: J P
authors: JP
authors: Gotteland
authors: E
authors: E
authors: Loumaye
authors: J
authors: J
authors: Donnez
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004715:Endometriosis / Q000378:metabolism* / Q000517:prevention & control; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors*; D014599:Uterus / Q000201:enzymology
chemical_list: C560930:estradiol-3-O-sulfamate; D004958:Estradiol; D043266:Steryl-Sulfatase