RT Journal Article
SR Electronic
T1 Transcriptional Regulation of Rat Hepatic Aryl Sulfotransferase (SULT1A1) Gene Expression by Glucocorticoids
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1130
OP 1135
VO 29
IS 8
A1 Zhengbo Duanmu
A1 Thomas A. Kocarek
A1 Melissa Runge-Morris
YR 2001
UL http://dmd.aspetjournals.org/content/29/8/1130.abstract
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