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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2010.1
- 수록면
- 731 - 738 (8page)
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초록· 키워드
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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 hERα 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.
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참고문헌 (24)
참고문헌 신청
Archer TK / 1986 / Kinetics of estrogendependent modulation of apolipoprotein A-I synthesis in human hepatoma cells / J Biol Chem 261 : 5067 ~ 5074
Assem M / 2004 / Interactions between hepatic Mrp4 and Sult2a as revealed by the constitutive androstane receptor and Mrp4 knockout mice / J Biol Chem 279 : 22250 ~ 22257
Beato M / 1989 / Gene regulation by steroid hormones / Cell 56 : 335 ~ 344
Blum A / 2001 / Selective ER modulator effects on serum lipoproteins and vascular function in postmenopausal women and in hypercholesterolemic men / Ann N Y Acad Sci 949 : 16
Blumberg B / 1998 / SXR, a novel steroid and xenobiotic-sensing nuclear receptor / Genes Dev 12 : 3195 ~ 3205
Assem M / 2004 / Interactions between hepatic Mrp4 and Sult2a as revealed by the constitutive androstane receptor and Mrp4 knockout mice / J Biol Chem 279 : 22250 ~ 22257
Beato M / 1989 / Gene regulation by steroid hormones / Cell 56 : 335 ~ 344
Blum A / 2001 / Selective ER modulator effects on serum lipoproteins and vascular function in postmenopausal women and in hypercholesterolemic men / Ann N Y Acad Sci 949 : 16
Blumberg B / 1998 / SXR, a novel steroid and xenobiotic-sensing nuclear receptor / Genes Dev 12 : 3195 ~ 3205
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