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Vol. 29, Issue 8, 1130-1135, August 2001

Transcriptional Regulation of Rat Hepatic Aryl Sulfotransferase (SULT1A1) Gene Expression by Glucocorticoids

Zhengbo Duanmu, Thomas A. Kocarek, and Melissa Runge-Morris

Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan

The 5'-flanking region [1892 base pairs (bp)] of the rat aryl sulfotransferase (SULT1A1) gene was cloned and the cis-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, 17beta -estradiol, and pregnenolone-16alpha -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.


Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics



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Copyright © 2001 by the American Society for Pharmacology and Experimental Therapeutics.