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A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis.
TLDR
A potent, nonsteroidal FXR ligand is used to show that FXR induces expression of small heterodimer partner 1 (SHP-1), an atypical member of the nuclear receptor family that lacks a DNA-binding domain that provides a molecular basis for the coordinate suppression of CYP7A1 and other genes involved in bile acid biosynthesis. Expand
Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis.
TLDR
It is demonstrated that fibroblast growth factor 15 signals from intestine to liver to repress the gene encoding cholesterol 7alpha-hydroxylase (CYP7A1), which catalyzes the first and rate-limiting step in the classical bile acid synthetic pathway. Expand
The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity
TLDR
It is proposed that PXR serves as a physiological sensor of LCA, and coordinately regulates gene expression to reduce the concentrations of this toxic bile acid, and suggest that PxR agonists may prove useful in the treatment of human cholestatic liver disease. Expand
Orphan Nuclear Receptors Constitutive Androstane Receptor and Pregnane X Receptor Share Xenobiotic and Steroid Ligands*
TLDR
It is demonstrated that several of the compounds that regulate mouse and human CAR, including natural steroids, bind directly to the receptors and suggest that CAR, like PXR, is a steroid receptor that is capable of recognizing structurally diverse compounds. Expand
Regulation of Multidrug Resistance-associated Protein 2 (ABCC2) by the Nuclear Receptors Pregnane X Receptor, Farnesoid X-activated Receptor, and Constitutive Androstane Receptor*
TLDR
It is demonstrated that MRP2 is regulated by three distinct nuclear receptor signaling pathways that converge on a common response element in the 5′-flanking region of this gene. Expand
The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module.
TLDR
The results provide evidence for the existence of a potent enhancer module, 8 kb distal to the transcription start point, which mediates the transcriptional induction of CYP3A4 by activators of hPXR and demonstrate cooperativity between elements within the distal enhancer region and cis-acting elements in the proximal promoter of CYp3A 4. Expand
Identification of a Novel Human Constitutive Androstane Receptor (CAR) Agonist and Its Use in the Identification of CAR Target Genes*
TLDR
It is reported that CAR and PXR activators differentially regulated the expression of several genes, demonstrating that these two nuclear receptors subserve overlapping but distinct biological functions in human hepatocytes. Expand
Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification.
TLDR
Evidence is provided that PXR regulates a similar program of genes involved in xenobiotic metabolism in human liver, and the importance of these two nuclear receptors in defending the body against a broad array of potentially harmful xenobiotics is underscore. Expand
St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor.
TLDR
It is shown that hyperforin, a constituent of St. John's wort with antidepressant activity, is a potent ligand for the pregnane X receptor, an orphan nuclear receptor that regulates expression of the cytochrome P450 (CYP) 3A4 monooxygenase. Expand
The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism.
TLDR
Although PXR evolved to protect the body, its activation by a variety of prescription drugs represents the molecular basis for an important class of harmful drug-drug interactions, so assays that detect PxR activity will be useful in developing safer prescription drugs. Expand
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