title: The selective vitamin D receptor agonist, elocalcitol, reduces endometriosis development in a mouse model by inhibiting peritoneal inflammation.
abstract: BACKGROUND
  Endometriosis, which is characterized by the growth of endometrial tissue at ectopic locations as well as vascular development and inflammation, is still an unmet clinical need since an optimal drug that allows for both pain and infertility management does not exist. Since both the eutopic and the ectopic endometrium express the vitamin D receptor (VDR), and VDR agonists are endowed with anti-proliferative and anti-inflammatory properties, we evaluated the effect of elocalcitol, a VDR agonist with low calcaemic liability, in a mouse model of experimentally induced endometriosis.
  
  
  RESULTS
  Endometriosis was induced by injection of syngeneic endometrial tissue fragments into adult Balb/c female mice. After having confirmed by immunohistochemistry that endometriotic lesions developing in mice expressed VDR, the mice were administered with elocalcitol (100 μg/kg) or vehicle orally, once a day, for various durations of time. In this model, elocalcitol was able to reduce total lesion weight up to 70% upon treatment for 1 week before and 2 weeks after disease induction. Interestingly, a therapeutic effect was also observed on already established lesions. Elocalcitol was shown to reduce the capacity of mouse endometrial cells to adhere to collagen. In addition in treated mice, a decreased state of peritoneal inflammation was demonstrated by the inhibition of macrophage recruitment and inflammatory cytokine secretion.
  
  
  CONCLUSIONS
  The VDR agonist elocalcitol inhibits lesion development in a validated mouse model of endometriosis, and exerts a protective effect on both the implantation and organization of transferred endometrial tissue. These preliminary data in mice provide a sound rationale for further testing in primate models and eventually in humans.
authors.affiliation: Center for Research in Obstetrics and Gynecology,  San Raffaele Scientific Institute, 20132 Milan,  Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Mariani
authors.forename: Paola
authors.initials: P
authors.lastname: Viganò
authors.forename: Davide
authors.initials: D
authors.lastname: Gentilini
authors.forename: Barbara
authors.initials: B
authors.lastname: Camisa
authors.forename: Elvira
authors.initials: E
authors.lastname: Caporizzo
authors.forename: Pietro
authors.initials: P
authors.lastname: Di Lucia
authors.forename: Antonella
authors.initials: A
authors.lastname: Monno
authors.forename: Massimo
authors.initials: M
authors.lastname: Candiani
authors.forename: Edgardo
authors.initials: E
authors.lastname: Somigliana
authors.forename: Paola
authors.initials: P
authors.lastname: Panina-Bordignon
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002448:Cell Adhesion; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004715:Endometriosis / Q000517:prevention & control*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D017737:Macrophages, Peritoneal / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010537:Peritoneum / Q000473:pathology*; D018167:Receptors, Calcitriol / Q000819:agonists* / Q000096:biosynthesis; D013997:Time Factors
chemical_list: C487049:BXL628; D016207:Cytokines; D018167:Receptors, Calcitriol; D007987:Gonadotropin-Releasing Hormone; D002117:Calcitriol