PT  - JOURNAL ARTICLE
AU  - Zhengbo Duanmu
AU  - Thomas A. Kocarek
AU  - Melissa Runge-Morris
TI  - Transcriptional Regulation of Rat Hepatic Aryl Sulfotransferase (SULT1A1) Gene Expression by Glucocorticoids
DP  - 2001 Aug 01
TA  - Drug Metabolism and Disposition
PG  - 1130--1135
VI  - 29
IP  - 8
4099  - http://dmd.aspetjournals.org/content/29/8/1130.short
4100  - http://dmd.aspetjournals.org/content/29/8/1130.full
SO  - Drug Metab Dispos2001 Aug 01; 29
AB  - The 5′-flanking region [1892 base pairs (bp)] of the rat aryl sulfotransferase (SULT1A1) gene was cloned and thecis-acting sequences involved in glucocorticoid-inducible SULT1A1 gene transcription were characterized. SULT1A1 promoter and 5′-flanking sequences lacked a TATA box and a consensus glucocorticoid response element. Using a 5′-rapid amplification of cDNA ends approach, four SULT1A1 transcription start sites were identified. Transient transfection studies with SULT1A1-5′:luciferase reporter constructs in primary cultured rat hepatocytes revealed that treatment with the potent glucocorticoid dexamethasone (10−9–10−5 M) produced concentration-dependent increases in luciferase activity in constructs containing from 1892 to 119 bp of the SULT1A1 5′-flanking region. Relative to the most upstream SULT1A1 transcription start site, the minimal cis-acting sequences that were required for dexamethasone-inducible SULT1A1 expression were located between −84 and −69 bp. Treatment of transfectants with a panel of steroids, including dexamethasone, triamcinolone acetonide, hydrocortisone, dihydrotestosterone, 17β-estradiol, and pregnenolone-16α-carbonitrile, revealed that steroid-inducible SULT1A1 gene expression was specific for glucocorticoid-class steroids. Concentration-response studies, coupled with a robust inhibition of glucocorticoid-inducible SULT1A1-5′:luciferase reporter activity by antiglucocorticoid/antiprogestin RU-486, recapitulated earlier findings on endogenous SULT1A1 gene expression and implicated a major role for the glucocorticoid receptor transcription factor in the regulation of glucocorticoid-inducible SULT1A1 gene expression. The American Society for Pharmacology and Experimental Therapeutics