HUMAN DEHYDROEPIANDROSTERONE SULFOTRANSFERASE GENE - MOLECULAR-CLONING AND STRUCTURAL CHARACTERIZATION

Dehydroepiandrosterone sulfotransferase (DHEA ST) catalyzes the sulfat e conjugation of DHEA and other steroids, From 20 to 25% of subjects a re included in a subgroup with high levels of hepatic DHEA ST activity , raising the possibility that this enzyme activity might be controlle d by a genetic polymorphism, To understand the molecular mechanisms in volved in regulating levels of DHEA ST activity in human tissue, we cl oned the human DHEA ST gene, STD, STD spans at least 17 kb and is comp osed of 6 exons and 5 introns, The locations of the splice junctions f or several of the introns are identical to those present in the rat ph enol or aryl ST gene, the only other cytosolic ST gene for which the e ntire exon/intron structure has been reported, as well as those presen t in two partially characterized genes for the rat senescence marker p rotein, genes that are also thought to encode ST enzymes, The 5'-flank ing region of the human STD gene does not contain canonical TATA or CC AAT elements, but this region is capable of promoting transcription of a reporter gene in Hep G2 cells. Molecular cloning and structural cha racterization of the human STD gene will make it possible to study gen etic mechanisms involved in the regulation of DHEA ST activity in huma n tissue.