oxytocin and Cholestasis--Intrahepatic

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-associated liver disease of unknown etiology. The aim of this study was to investigate the change in maternal and fetal adrenal function in clinical and experimental ICP.. The maternal and fetal serum levels of cortisol and dehydroepiandrosterone sulfate (DHEAS) were determined in 14 women with ICP and in pregnant rats with estrogen-induced intrahepatic cholestasis.. In women with ICP, the fetal serum cortisol and DHEAS levels were significantly higher than those in women with normal pregnancy, after correcting the impact of gestational age at delivery. The relationship between fetal cortisol and maternal cholic acid levels was bidirectional; the fetal cortisol tended to increase in mild ICP, while it decreased in severe ICP. In pregnant rats with estrogen-induced cholestasis, the fetal cortisol level was significantly lower in the group with oxytocin injection, compared with the group without oxytocin injection (191.92±18.86 vs. 272.71±31.83 ng/ml, P<0.05). In contrast, the fetal cortisol concentration was increased after oxytocin injection in normal control rats.. The data indicate that fetal stress-responsive system is stimulated in mild ICP, but it is suppressed in severe ICP, which might contribute to the occurrence of unpredictable sudden fetal death. Further studies are warranted to explore the role of impaired fetal adrenal function in the pathogenesis of ICP and the clinical implications.

Topics: Adrenal Glands; Adult; Animals; Case-Control Studies; Cholestasis, Intrahepatic; Cholic Acid; Dehydroepiandrosterone Sulfate; Delivery, Obstetric; Female; Fetus; Humans; Hydrocortisone; Liver Function Tests; Oxytocin; Pregnancy; Rats; Rats, Sprague-Dawley

We tested the hypothesis that during intrahepatic cholestasis of pregnancy bile acids activate the myometrial oxytocin receptor pathway.. 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.. 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).. 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.

Topics: Adult; Cells, Cultured; Cholestasis, Intrahepatic; Cholic Acid; Dose-Response Relationship, Drug; Female; Humans; In Vitro Techniques; Myometrium; Oxytocin; Pregnancy; Pregnancy Complications; Receptors, Oxytocin; RNA, Messenger; Uterine Contraction

Prematurity and fetal death are common complications in patients with cholestasis of pregnancy. Both conditions appear to be associated with abnormal patterns of uterine activity. We studied the oxytocin-induced contractile activity in uterine strips taken from patients with cholestasis of pregnancy (n = 6) and from women with normal pregnancy (n = 6). Contractile activity of the myometrium in response to oxytocin was significantly higher in patients with cholestasis of pregnancy than in normally pregnant patients, at doses of 10(-6), 10(-4), and 10(-2) M. We found that there is a greater maximal response to oxytocin in strips of myometrium from patients with cholestasis of pregnancy than from normally pregnant patients.

Topics: Cholestasis, Intrahepatic; Female; Humans; In Vitro Techniques; Oxytocin; Pregnancy; Pregnancy Complications; Uterine Contraction