title: Estrogen receptor α antagonists mediate changes in CCL20 and CXCL1 secretions in the murine female reproductive tract.
abstract: OBJECTIVE
  Estradiol regulates chemokine secretion from uterine epithelial cells, but little is known about estradiol regulation in vivo or the role of estrogen receptors (ERs).
  
  
  METHODS
  CCL20 and CXCL1 present in reproductive washes following treatment with selective estrogen receptor modulators (SERMs) were compared with that during estrous and following estradiol-treated ovariectomized BALB/c mice. Cellular regulation was determined using isolated vaginal and uterine epithelial/stromal cells in vitro.
  
  
  RESULTS
  Uterine and vaginal chemokine secretion is cyclically regulated with CCL20 at low levels but CXCL1 at high levels during high estradiol, generally mimicking estradiol effect in vivo. ERα but not ERβ regulated CCL20/CXCL1 secretion by uterine epithelial cells in vitro and vaginal CCL20 in vivo. Estradiol/SERMs failed to alter uterine CCL20 secretion in ovariectomized mice. Diminished uterine epithelial ERα staining following ovariectomy corresponded with estradiol unresponsiveness of uterine tissue.
  
  
  CONCLUSIONS
  Estrogen receptors α regulates CCL20/CXCL1 secretion in the female reproductive tract, and ERα antagonists directly oppose the regulation by estradiol. Understanding ER-mediated antimicrobial chemokine expression is important to elucidate cyclic susceptibility to sexually transmitted pathogens.
authors.affiliation: Department of Physiology, Dartmouth Medical School, Lebanon, NH, USA. Danica.Hickey@PHSA.ca
authors.forename: Danica K
authors.initials: DK
authors.lastname: Hickey
authors.forename: John V
authors.initials: JV
authors.lastname: Fahey
authors.forename: Charles R
authors.initials: CR
authors.lastname: Wira
mesh_terms: D000818:Animals; D054418:Chemokine CCL20 / Q000378:metabolism*; D054360:Chemokine CXCL1 / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D013329:Structure-Activity Relationship; D014599:Uterus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014621:Vagina / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: C493447:CCL20 protein, mouse; D054418:Chemokine CCL20; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D004958:Estradiol