title: Estrogen receptor-beta mediates cyclooxygenase-2 expression and vascular prostanoid levels in human placental villous endothelial cells.
abstract: OBJECTIVE
  Regulation of fetoplacental blood flow is likely mediated by factors such as prostanoids. Estrogen and its receptors affect prostanoid biosynthesis. Previously, we demonstrated that villous endothelial cells express estrogen receptor-beta (ESR2), and we sought to determine its role in the mediation of fetoplacental vascular function.
  
  
  METHODS
  Villous endothelial cells from uncomplicated pregnancies were isolated, cultured, and treated with estrogen. RNA interference, real-time polymerase chain reaction, Western blotting, and enzyme immunoassays were performed.
  
  
  RESULTS
  Cyclooxygenase-2 (COX-2) expression levels were not altered consistently by estrogen. RNA interference of ESR2 led to a concomitant decrease in COX-2 messenger RNA (P < .0001) and protein (P < .05) in the presence and absence of estradiol. ESR2 knock-down also led to diminished prostacyclin and thromboxane concentrations in the absence of estradiol (P < .005).
  
  
  CONCLUSIONS
  ESR2 mediates COX-2 expression levels and both prostacyclin and thromboxane concentrations in the basal state, which suggests the possibility of ligand-independent regulation of COX-2 activity and prostaglandin H2 substrate availability. Further investigation regarding ESR2 regulation of prostanoid biosynthesis and its effects on the fetoplacental vasculature is warranted.
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Su
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Lin
authors.forename: Rana
authors.initials: R
authors.lastname: Zeine
authors.forename: Ping
authors.initials: P
authors.lastname: Yin
authors.forename: Scott
authors.initials: S
authors.lastname: Reierstad
authors.forename: Joy E
authors.initials: JE
authors.lastname: Innes
authors.forename: Serdar E
authors.initials: SE
authors.lastname: Bulun