Farnesoid X receptor, FXR

STD has also been shown to be regulated by farnesoid X receptor (FXR) [34], CAR [35] and liver X receptor (LXR) [36]. Interestingly, all four receptors share the same IR-0 response element to regulate the expression of this S ULT isoform. The hierarchy and relative contribution of individual nuclear receptors in Sult2a regulation remain to be determined. 

Farnesoid X receptor (FXR) and liver X receptors (LXRs) belong to the same NR family as PXR and CAR. Their primary role lies in cholesterol and bile acid metabolism regulation. Like many NRs of this family, FXR heterodimerizes with RXR in vivo [46]. 

Bile acids are also natural ligands for the farnesoid X receptor (FXR), a receptor that belongs to the nuclear hormone receptor superfamily. The hydrophobic bile acid chenodeoxycholic acid (CDCA) is the most potent... 

The farnesoid X receptor is a member of the class of nuclear hormone receptors, which have key roles in development and homeostasis, as well as in many diseases like obesity, diabetes and cancer. The farnesoid X receptor shows structural similarity to the estrogen receptor (ER ), which mediates a broad spectrum of physiological functions such as regulation of reproduction, modulation of bone density, cholesterol transport and breast cancer. The farnesoid X receptor also shows similarity with the peroxisome proliferation-activated receptor y (PPARy), which is involved in fat metabolism, inflammatory and immune responses. The estrogen receptor (ER ), the peroxisome proliferation-activated receptor y (PPARy) and the farnesoid X receptor (FXR) can be clustered in a... 

In such a reverse endocrinology approach the farnesoid X receptor (FXR) could be connected to bile acid ligands. By further exploration of bile acids and other chemical probes for FXR it was discovered that FXR is linked to bile acid homeostasis, and it was postulated that FXR ligands might have beneficial effects for the treatment of cholestatic liver disease and other disorders [50]. 

Bile acids and metabolites are endogenous PXR ligands that activate PXR to metabolize bile acids [49]. This may be a mechanism for detoxifying bile acids in the liver and intestine [50]. Bile acids activate farnesoid X receptor (FXR), which induces expression of small heterodimer partner (SHP), an atypical orphan receptor that lacks the DBD. SHP then inhibits transactivation of CYP7A1 gene by orphan... 

In addition to PXR and CAR, several other nuclear receptors, such as vitamin D receptor (VDR), hepatocyte nuclear factor 4a (HNF4a), peroxisome proliferator-activated receptors (PPARs), and farnesoid X receptor (FXR), have also been implicated in the regulation of xenobiotic enzymes and transporters [9-12], More recently, results from our lab have shown that the liver X receptor (LXR), a previously known sterol sensor, can also regulate the expression of phase II SULTs, such as the bile acid detoxifying hydroxysteroid sulfotransferase Sult2a9/2al [13] and the estrogen sulfotransferase (Est/Sultlel) [14],... 

In another study, 42,000 compounds were screened in three different versions of a farnesoid X receptor (FXR) antagonism assay. AlphaScreen, time resolved fluorescence (TRF), and time resolved FRET (TR-FRET) were used. These identified 104, 23, and 57 actives, respectively. Only 18 compounds were identified by all three methods. Further cellular testing showed that only about 30% of them were functionally active, with AlphaScreen identifying more of the functionally active compounds than the other two methods. This group also found that screening mixtures rather than discrete compounds was more likely to result in both false positives and false negatives. ... 

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