title: Bile acids increase response and expression of human myometrial oxytocin receptor.
abstract: OBJECTIVE
  We tested the hypothesis that during intrahepatic cholestasis of pregnancy bile acids activate the myometrial oxytocin receptor pathway.
  
  
  METHODS
  Myometrial sensitivity to oxytocin and oxytocin-receptor messenger RNA and protein level was investigated. The ability of cholic acid to mediate such changes was evaluated.
  
  
  RESULTS
  Cholestasis patients required lesser oxytocin to elicit four uterine contractions in 10 minutes (1.3+/-0.6 vs 3.6+/-0.8 U, P<.05, n=7) and had lower in vitro ED(50) (1.6 x 10(-10) mol/L vs 1.0 x 10(-8) mol/L, P<.05, n=7) than controls. The 24-hour incubation of control myometrial strips (n=7) with cholic acid (20 micromol/L) increased oxytocin sensitivity. Incubation of cultured myometrial cells (n=5) with cholic acid increased oxytocin-receptor expression (messenger RNA and protein).
  
  
  CONCLUSIONS
  We demonstrate that during intrahepatic cholestasis of pregnancy, an activation of the oxytocin receptor pathway occurs. This event seems to be the result of a cholic acid-mediated increase in oxytocin-receptor expression.
authors.affiliation: Department of Obstetrics and Gynecology, Pontificia Universidad Católica de Chile School of Medicine, Santiago, Chile.
authors.forename: Alfredo M
authors.initials: AM
authors.lastname: Germain
authors.forename: Sumie
authors.initials: S
authors.lastname: Kato
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Carvajal
authors.forename: Guillermo J
authors.initials: GJ
authors.lastname: Valenzuela
authors.forename: Gloria L
authors.initials: GL
authors.lastname: Valdes
authors.forename: Juan C
authors.initials: JC
authors.lastname: Glasinovic
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002780:Cholestasis, Intrahepatic / Q000378:metabolism*; D019826:Cholic Acid / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism*; D010121:Oxytocin / Q000008:administration & dosage; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism*; D014590:Uterine Contraction
chemical_list: D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D010121:Oxytocin; D019826:Cholic Acid