PT  - JOURNAL ARTICLE
AU  - Fang, Hai-Lin
AU  - Abdolalipour, Masumeh
AU  - Duanmu, Zhengbo
AU  - Smigelski, Jeffrey R.
AU  - Weckle, Amy
AU  - Kocarek, Thomas A.
AU  - Runge-Morris, Melissa
TI  - REGULATION OF GLUCOCORTICOID-INDUCIBLE HYDROXYSTEROID SULFOTRANSFERASE (SULT2A-40/41) GENE TRANSCRIPTION IN PRIMARY CULTURED RAT HEPATOCYTES: ROLE OF CCAAT/ENHANCER-BINDING PROTEIN LIVER-ENRICHED TRANSCRIPTION FACTORS
AID  - 10.1124/dmd.104.000281
DP  - 2005 Jan 01
TA  - Drug Metabolism and Disposition
PG  - 147--156
VI  - 33
IP  - 1
4099  - http://dmd.aspetjournals.org/content/33/1/147.short
4100  - http://dmd.aspetjournals.org/content/33/1/147.full
SO  - Drug Metab Dispos2005 Jan 01; 33
AB  - The mechanism responsible for glucocorticoid receptor (GR)-mediated induction of rat hepatic hydroxysteroid sulfotransferase (SULT2A-40/41) gene transcription was investigated. We previously reported that the region of the SULT2A-40/41 5′-flanking region delimited by -158 to -77 nucleotides relative to the transcription start site was sufficient to support GR-inducible expression. This region of the SULT2A-40/41 gene does not contain a consensus glucocorticoid receptor-responsive element, but does contain two consensus sites for liver-enriched CCAAT/enhancer-binding protein (C/EBP) transcription factors. In the present study, incubation of primary cultured rat hepatocytes with a GR-activating concentration (10-7 M) of a potent glucocorticoid, dexamethasone or triamcinolone acetonide (TA), rapidly produced increases in C/EBPα and C/EBPβ nuclear protein contents, as measured by Western blot or in vitro DNA-binding activity analysis, that preceded increases in SULT2A-40/41 mRNA and protein levels. Transient cotransfection of SULT2A-40/41 reporter plasmids with a dominant negative C/EBP expression plasmid completely blocked TA-inducible SULT2A-40/41 reporter gene expression. Linker scanning and site-directed mutagenesis of the proximal SULT2A-40/41 5′-flanking region, complemented by in vitro DNA-binding analyses, indicated that the more distal C/EBP site was important for controlling SULT2A-40/41 promoter activity. These data support a role for GR-inducible C/EBPα and C/EBPβ expression in the transactivation of hepatic SULT2A-40/41 expression. The American Society for Pharmacology and Experimental Therapeutics