title: Estrogen modulates transactivations of SXR-mediated liver X receptor response element and CAR-mediated phenobarbital response element in HepG2 cells.
abstract: The nuclear receptors, steroid and xenobiotic receptor (SXR) and constitutive androstane receptor (CAR) play important functions in mediating lipid and drug metabolism in the liver. The present study demonstrates modulatory actions of estrogen in transactivations of SXR-mediated liver X receptor response element (LXRE) and CAR-mediated phenobarbital response element (PBRU). When human estrogen receptor (hERα) and SXR were exogenously expressed, treatment with either rifampicin or corticosterone promoted significantly the SXR-mediated transactivation of LXRE reporter gene in HepG2. However, combined treatment with estrogen plus either rifampicin or corticosterone resulted in less than 50% of the mean values of the transactivation by rifampicin or corticosterone alone. Thus, it is suggested that estrogen may repress the SXR-mediated transactivation of LXRE via functional cross-talk between ER and SXR. The CAR-mediated transactivation of PBRU was stimulated by hERa in the absence of estrogen. However, the potentiation by CAR agonist, TCPOBOP, was significantly repressed by moxestrol in the presence of ER. Thus, ER may play both stimulatory and inhibitory roles in modulating CAR-mediated transactivation of PBRU depending on the presence of their ligands. In summary, this study demonstrates that estrogen modulates transcriptional activity of SXR and CAR in mediating transactivation of LXRE and PBRU, respectively, of the nuclear receptor target genes through functional cross-talk between ER and the corresponding nuclear receptors.
authors.affiliation: Department of Pharmaceutical Engineering, Jinju National University, Jinju 660-758, Korea. g-min@jinju.ac.kr
authors.forename: Gyesik
authors.initials: G
authors.lastname: Min
mesh_terms: D000090702:Constitutive Androstane Receptor; D003345:Corticosterone / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism*; D004997:Ethinyl Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism*; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D010634:Phenobarbital / Q000378:metabolism; D000077297:Pregnane X Receptor; D011725:Pyridines / Q000494:pharmacology; D020239:Receptor Cross-Talk; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D020218:Response Elements; D012293:Rifampin / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects* / Q000502:physiology
chemical_list: D000090702:Constitutive Androstane Receptor; D004967:Estrogens; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D000077297:Pregnane X Receptor; D011725:Pyridines; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D004997:Ethinyl Estradiol; C011310:moxestrol; C028474:1,4-bis(2-(3,5-dichloropyridyloxy))benzene; D012293:Rifampin; D003345:Corticosterone; D010634:Phenobarbital