Transcriptional regulation of rat hepatic aryl sulfotransferase (SULT1A1) gene expression by glucocorticoids

The 5'-flanking region [1892 base pairs (bp)] of the rat aryl sulfo-transfe rase (SULT1A1) gene was cloned and the cis-acting sequences involved in glu cocorticoid-inducible SULT1A1 gene transcription were characterized, SULT1A 1 promoter and 5'-flanking sequences lacked a TATA box and a consensus gluc ocorticoid response element. Using a 5'-rapid amplification of cDNA ends ap proach, four SULT1A1 transcription start sites were identified, Transient t ransfection studies with SULT1A1 -5':luciferase reporter constructs in prim ary cultured rat hepatocytes revealed that treatment with the potent glucoc orticoid dexamethasone (10(-9)-10(-5) M) produced concentration-dependent i ncreases in luciferase activity in constructs containing from 1892 to 119 b p of the SULT1A1 5'-flanking region. Relative to the most upstream SULT1A1 transcription start site, the minimal cis-acting sequences that were requir ed 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 , 17 beta -estradiol, and pregnenolone-16 alpha -carbonitrile, revealed tha t steroid-inducible SULT1A1 gene expression was specific for glucocorticoid -class steroids. Concentration-response studies, coupled with a robust inhi bition 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 glucocort icoid-inducible SULT1A1 gene expression.