PT  - JOURNAL ARTICLE
AU  - Keith R. Stayrook
AU  - Pamela M. Rogers
AU  - Rajesh S. Savkur
AU  - Yongjun Wang
AU  - Chen Su
AU  - Gabor Varga
AU  - Xin Bu
AU  - Tao Wei
AU  - Sunil Nagpal
AU  - Xiaole Shirley Liu
AU  - Thomas P. Burris
TI  - Regulation of Human 3α-Hydroxysteroid Dehydrogenase (AKR1C4) Expression by the Liver X Receptor α
AID  - 10.1124/mol.107.039099
DP  - 2008 Feb 01
TA  - Molecular Pharmacology
PG  - 607--612
VI  - 73
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/73/2/607.short
4100  - http://molpharm.aspetjournals.org/content/73/2/607.full
SO  - Mol Pharmacol2008 Feb 01; 73
AB  - Type I human hepatic 3α-hydroxysteroid dehydrogenase (AKR1C4) plays a significant role in bile acid biosynthesis, steroid hormone metabolism, and xenobiotic metabolism. Utilization of a hidden Markov model for predictive modeling of nuclear hormone receptor response elements coupled with chromatin immunoprecipitation/microarray technology revealed a putative binding site in the AKR1C4 promoter for the nuclear hormone receptor known as liver X receptor α, (LXRα [NR1H3]), which is the physiological receptor for oxidized cholesterol metabolites. The putative LXRα response element (LXRE), identified by chromatin immunoprecipitation, was ∼1.5 kilobase pairs upstream of the transcription start site. LXRα was shown to bind specifically to this LXRE and mediate transcriptional activation of the AKR1C4 gene, leading to increased AKR1C4 protein expression. These data suggest that LXRα may modulate the bile acid biosynthetic pathway at a unique site downstream of CYP7A1 and may also modulate the metabolism of steroid hormones and certain xenobiotics. The American Society for Pharmacology and Experimental Therapeutics