title: Corticotropin-releasing hormone expression in patients with intrahepatic cholestasis of pregnancy after ursodeoxycholic acid treatment: an initial experience.
abstract: OBJECTIVE
  Corticotropin-releasing hormone (CRH) is one of the most potent vasodilatory factors in the human feto-placental circulation. The expression of CRH was significantly down-regulated in patients with intrahepatic cholestasis of pregnancy (ICP).
  
  
  METHODS
  One hundred pregnant women diagnosed with ICP at 34-34(+6) weeks of gestation agreed to participate in this prospective nested case-control study. Thirty ICP patients were finally recruited in this study, with 16 cases in the ursodeoxycholic acid (UDCA) group (UDCA 750 mg/d) and 14 cases in the control group (Transmetil 1000 mg/d or Essentiale 1368 mg/d). Maternal serum samples were obtained in diagnosis and at 37-37(+6) weeks of gestation. Placental tissues were obtained from participants after delivery. ELISA, enzymatic colorimetric and Western blotting were used to evaluate the concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA) and CRH in maternal serum and expression of CRH in placenta tissues.
  
  
  RESULTS
  The UDCA group had greater reduction in maternal serum ALT, AST and TBA levels in ICP patients (all p < 0.01). Maternal serum CRH concentrations in the UDCA group after treatment (122.10 ± 44.20) pg/ml was significantly higher than pretreatment (95.45 ± 26.47) pg/ml (p < 0.01). After treatment, maternal serum CRH concentrations of the UDCA group (122.10 ± 44.20) pg/ml was significantly higher than in the control group (80.71 ± 41.10) pg/ml (p < 0.01). Placental CRH expression in the UDCA group (2.79 ± 1.72) was significantly higher than in the control group (0.69 ± 0.36) (p < 0.01).
  
  
  CONCLUSIONS
  Maternal serum and placental CRH expression in ICP patients were up-regulated after treatment of UDCA. The up-regulation of CRH expression after UDCA treatment may play an important role in the therapeutic mechanism of ICP. All patients recruited in this study had severe cholestasis (TBA ≥ 40 µmol/L). Further studies are warranted in different gestational weeks and TBA levels to provide more evidence for the correlation between UDCA treatment and CRH expression in ICP patients.
authors.affiliation: Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education , Chengdu, Sichuan , China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Mao Mao
authors.initials: MM
authors.lastname: He
authors.forename: Zheng Fei
authors.initials: ZF
authors.lastname: Liu
authors.forename: Bing Xin
authors.initials: BX
authors.lastname: Gao
authors.forename: Xiao Dong
authors.initials: XD
authors.lastname: Wang
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D002780:Cholestasis, Intrahepatic / Q000188:drug therapy* / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000378:metabolism; D011446:Prospective Studies; D016896:Treatment Outcome; D015854:Up-Regulation; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D001647:Bile Acids and Salts; D015415:Biomarkers; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D003346:Corticotropin-Releasing Hormone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Corticotropin-releasing hormone; Intrahepatic cholestasis of pregnancy; Placenta; Ursodeoxycholic acid