title: The Interaction of PPARα and CYP7B1 with ERα, β Impacted the Occurrence and Development of Intrahepatic Cholestasis in Pregnant Rats.
abstract: Intrahepatic cholestasis of pregnancy (ICP) is a disorder of bile acid (BA) synthesis, excretion, and metabolism, with systemic accumulation of BAs, which can lead to prematurity, fetal distress, and intrauterine death. Here, we investigate the expression of peroxisome proliferator-activated receptor alpha and cytochrome P450 oxysterol 7alpha-hydroxylase by exposing to 17α-ethynylestradiol with or without the estrogen receptor signaling pathway in pregnant rats with intrahepatic cholestasis. In vivo and in vitro evidences showed that estrogen receptor alpha (ERα) may be the key point of occurrence and development of intrahepatic cholestasis in pregnant rats. Besides, the abnormalities in genes could be reversed by ERα small interfering RNA. Our findings provide the ERα-centered hypothesis on the mechanisms of ICP. New perspectives are emerging for the treatment of estrogen-induced hepatic complication.
authors.affiliation: 1 Department of Obstetrics and Gynecology, Ninth School of Clinical Medicine, Peking University, Beijing, China.
authors.forename: Zhaoyi
authors.initials: Z
authors.lastname: Song
authors.affiliation: 2 Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Shi
mesh_terms: D000818:Animals; D002780:Cholestasis, Intrahepatic / Q000378:metabolism*; D000072474:Cytochrome P450 Family 7 / Q000235:genetics / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D047493:PPAR alpha; D034741:RNA, Small Interfering; D004997:Ethinyl Estradiol; D013250:Steroid Hydroxylases; D000072474:Cytochrome P450 Family 7; C490784:Cyp7b1 protein, rat
keywords: 17α-ethynylestradiol; estrogen receptor alpha; estrogen receptor beta; intrahepatic cholestasis of pregnancy; oxysterol 7alpha-hydroxylase; peroxisome proliferator-–activated receptor alpha; small interfering RNA