Expression of corticotrophin-releasing hormone and its receptor in patients with intrahepatic cholestasis of pregnancy

Objective: Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-specific liver disorders. Although various biological effects of corticotrophin-releasing hormone (CRH) has in pregnancy have been reported, its activities in patients with ICP are lacking. Here we evaluated CRH and its receptor (CRH-R1) expression in placenta and serum in control and ICP patients, to assess their potential activities in the ICP pathogenesis. Methods and materials: Placental tissues were obtained from the control and ICP patients (10 cases for each group) between 37 and 39 gestational weeks. Immunohistochemistry, Western Blotting and real-time PCR analysis were used to detect the CRH and CRH-R1 expression in placenta. Meanwhile, maternal serums were analyzed for detecting CRH in the control and ICP patients (80 cases for each group) in 34-37 gestational weeks. All data were observed and recorded for comparing and analyzing in control and ICP patients. Results: CRH staining was found in syncytiotrophoblast and feto-placental vascular endothelium cells of placenta, whereas CRH-R1 staining was found in syncytiotrophoblast by using immunohistochemical analysis. The CRH expression level in ICP placenta was significantly lower than those results in controls (P < 0.01). For CRH-R1, CRH mRNA and CRH-R1 mRNA expressions, no statistical differences were found between control and ICP groups (all P > 0.05). Serum CRH levels increased in both control and ICP groups, but the growth rate was limited in ICP group, especially in late pregnancy (P < 0.05). Conclusions: The down-regulation of CRH in ICP placentas and the limited growth rate of CRH in the maternal serum of ICP patients might impair the blood flow regulation of the utero-placental-fetal unit, which might result in poor fetoplacental vascular perfusion and adverse pregnancy outcomes. CRH might play a significant role in the pathogenesis of ICP and provide a new approach to further investigate the etiology of ICP. (C) 2013 Elsevier Ltd. All rights reserved.