Bile acids increase response and expression of human myometrial oxytocin receptor
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Date
2003
Journal Title
Journal ISSN
Volume Title
Publisher
MOSBY, INC
Abstract
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.
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.
Description
Keywords
intrahepatic cholestasis of pregnancy, oxytocin receptor, INTRA-HEPATIC CHOLESTASIS, INTRAHEPATIC CHOLESTASIS, OBSTETRIC CHOLESTASIS, UTERINE ACTIVITY, PREGNANT-WOMEN, MESSENGER-RNA, CHOLIC-ACID, DECIDUA, PROTEIN, CELLS