Abu-Hayyeh et al. have shown that levels of epiallopregnanolone sulphate—a sulphated progesterone metabolite—are above normal in patients with intrahepatic cholestasis of pregnancy. At these levels, epiallopregnanolone sulphate acted as a partial agonist for the farnesoid X receptor (FXR), mediating expression of bile acid homeostasis genes. Bile acid mediated recruitment of co-factor motifs to the FXR ligand binding domain was competitively inhibited by epiallopregnanolone sulphate.
ORIGINAL RESEARCH PAPER
Abu-Hayyeh, S. et al. Intrahepatic cholestasis of pregnancy levels of sulfated progesterone metabolites inhibit FXR resulting in a pro-cholestatic phenotype. Hepatology doi:10.1002/hep.26055
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Linking abnormal bile acid homeostasis and endocrine component of intrahepatic cholestasis of pregnancy. Nat Rev Gastroenterol Hepatol 9, 616 (2012). https://doi.org/10.1038/nrgastro.2012.188
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DOI: https://doi.org/10.1038/nrgastro.2012.188