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Submitted on August 29, 2003
Accepted on September 14, 2004
University of Texas Southwestern Medical Center, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Dallas, Texas; Tohuku University School of Medicine, Department of Pathology, Sendai, Japan, King's College London, London, UK and University of Pennsylvania Medical Center, Center for Research on Reproduction and Women's Health, Philadelphia, Pennsylvania
* To whom correspondence should be addressed. E-mail: william.rainey{at}utsouthwestern.edu.
Sulfonation is a Phase II conjugation reaction responsible for the biotransformation of many compounds including steroids, bile acids, and drugs. Humans are presently known to express at least five cytosolic sulfotransferase (SULT) enzymes, of which only two are hydroxysteroid SULT, SULT2A1, commonly known as steroid sulfotransferase and the cholesterol sulfotransferase, SULT2B1. SULT2A1 is highly expressed in the adrenal where it is responsible for the sulfation of hydroxysteroids including conversion of DHEA to DHEA-S and in the liver where it is responsible for sulfation of bile acids and circulating hydroxysteroids. Little is known concerning the transcriptional regulation of human SULT2A1 in adrenal. Herein we demonstrate the role of two transcription factors, steroidogenic factor 1 (SF1) and GATA-6, in the regulation of SULT2A1 transcription. These transcription factors were quantified by real-time RTPCR in normal human adrenal tissue. Transient transfection assays with deleted and mutated SULT2A1 promoter constructs allowed for the determination of specific SF1 and GATA binding cis-regulatory elements necessary for transactivation of SULT2A1 promoter and binding was confirmed by EMSA analysis. Both SF1 and GATA-6 were positive regulators of SULT2A1 promoter constructs. These data support the hypothesis that adrenal SULT2A1 expression is regulated by SF1 and GATA-6.
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