Bile acids increase response and expression of human myometrial oxytocin receptor.
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.
Germain
Alfredo M
AM
Department of Obstetrics and Gynecology, Pontificia Universidad Católica de Chile School of Medicine, Santiago, Chile.
Kato
Sumie
S
Carvajal
Jorge A
JA
Valenzuela
Guillermo J
GJ
Valdes
Gloria L
GL
Glasinovic
Juan C
JC
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
D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D010121:Oxytocin; D019826:Cholic Acid