RT Journal Article
SR Electronic
T1 TRANSACTIVATION OF GLUCOCORTICOID-INDUCIBLE RAT ARYL SULFOTRANSFERASE (SULT1A1) GENE TRANSCRIPTION
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1378
OP 1381
DO 10.1124/dmd.31.11.1378
VO 31
IS 11
A1 Hai-Lin Fang
A1 Sarita Shenoy
A1 Zhengbo Duanmu
A1 Thomas A. Kocarek
A1 Melissa Runge-Morris
YR 2003
UL http://dmd.aspetjournals.org/content/31/11/1378.abstract
AB The purpose of the current study was to establish the role of the glucocorticoid receptor (GR) and androgen receptor (AR) transcription factors in the transactivation of rat aryl sulfotransferase (SULT1A1) gene transcription and to identify the functional hormone-responsive element(s) in the SULT1A1 gene. A cis-acting inverted repeat with three intervening bases (IR3) was identified in the 5′-flanking of the SULT1A1 gene that mediates the transactivation of SULT1A1 gene transcription by both the GR and AR. CV-1 cells were cotransfected with SULT1A1-luciferase reporter plasmids and either wild-type or mutant GR or AR expression constructs. In cotransfectants expressing the wild-type GR, treatment with triamcinolone acetonide produced an ∼4- to 6-fold induction of luciferase activity in IR3-containing SULT1A1 reporter plasmids. IR3-containing SULT1A1 reporter constructs were also activated by treatment with the synthetic androgen R1881 in cells cotransfected with wild-type but not mutant AR. In primary cultured rat hepatocytes, androgen-inducible expression of IR3-containing SULT1A1 reporter plasmids required cotransfection with AR expression plasmid. Targeted disruption of the SULT1A1 IR3 by mutation of a conserved GT sequence in the 3′ half-site of the element ablated GR and AR responsiveness. These results indicate that a proximal IR3 element in the 5′-flanking region of the rat SULT1A1 gene is sufficient for the transactivation of SULT1A1 gene transcription by the GR and AR, and that relative to the GR, functional AR activity is reduced in primary cultured rat hepatocytes. The American Society for Pharmacology and Experimental Therapeutics