title: Intact progesterone receptors are essential to counteract the proliferative effect of estradiol in a genetically engineered mouse model of endometriosis.
abstract: OBJECTIVE
  To determine the role of P and its nuclear receptor PR in the growth of ectopic uterine tissue of mice with or without a disrupted PR gene.
  
  
  METHODS
  Animal study.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  Female wild-type (WT) and transgenic knockout mice for P receptor (PRKO).
  
  
  METHODS
  Endometriosis was induced in the following groups of ovariectomized adult mice: [1] untreated WT, [2] estradiol (E(2))-treated WT, [3] P-treated WT, [4] E(2) + P-treated WT, [5] untreated PRKO, [6] E(2)-treated PRKO, and [7] E(2) + P-treated PRKO (n = 5 in each group).
  
  
  METHODS
  The size of ectopic uterine tissue in WT and PRKO mice were compared between the groups subjected to treatments with P or E(2). Tissue proliferating cell nuclear antigen (PCNA) levels were compared among these groups.
  
  
  RESULTS
  Treatment with P only significantly decreased the size of WT ectopic uterine tissue. The untreated PRKO ectopic uterine tissue was significantly larger than WT tissue. Estradiol increased the size of ectopic uterine tissues, and this E(2)-dependent growth could be suppressed by P in WT tissues but not in PRKO tissues. Finally, the hormone-dependent changes in ectopic uterine tissue size were accompanied by comparable alterations in PCNA levels.
  
  
  CONCLUSIONS
  Intact PR in ectopic uterine tissue is essential to abolish E(2)-dependent or -independent proliferation. We also suggest that ectopic uterine tissue is associated with significantly increased resistance to P action and increased predisposition to E(2)-dependent proliferation in the absence of PR. Overall, these findings support the hypothesis that P resistance in human endometriosis may be due to the absence of sufficient levels of functional PR in this tissue.
authors.affiliation: Department of Obstetrics and Gynecology, Northwestern University, 333 East Superior Street, Chicago, IL 60611, USA.
authors.forename: Zongjuan
authors.initials: Z
authors.lastname: Fang
authors.forename: Sijun
authors.initials: S
authors.lastname: Yang
authors.forename: John P
authors.initials: JP
authors.lastname: Lydon
authors.forename: Franco
authors.initials: F
authors.lastname: DeMayo
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Tamura
authors.forename: Bilgin
authors.initials: B
authors.lastname: Gurates
authors.forename: Serdar E
authors.initials: SE
authors.lastname: Bulun
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004715:Endometriosis / Q000235:genetics / Q000473:pathology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011980:Receptors, Progesterone / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D011980:Receptors, Progesterone; D004958:Estradiol