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. STUDY DESIGN: 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 J, P < .05, n = 7) and had lower in vitro ED50 (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 mmol/L) increased oxytocin sensitivity. Incubation of cultured myometrial cells (n = 5) with cholic acid increased oxytocin-receptor expression (messenger RNA and protein). CONCLUSION: 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.