RT Journal Article
SR Electronic
T1 Regulation of Human 3α-Hydroxysteroid Dehydrogenase (AKR1C4) Expression by the Liver X Receptor α
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 607
OP 612
DO 10.1124/mol.107.039099
VO 73
IS 2
A1 Keith R. Stayrook
A1 Pamela M. Rogers
A1 Rajesh S. Savkur
A1 Yongjun Wang
A1 Chen Su
A1 Gabor Varga
A1 Xin Bu
A1 Tao Wei
A1 Sunil Nagpal
A1 Xiaole Shirley Liu
A1 Thomas P. Burris
YR 2008
UL http://molpharm.aspetjournals.org/content/73/2/607.abstract
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