Molecular cloning and functions of rat liver hydroxysteroid sulfotransferases catalysing covalent binding of carcinogenic polycyclic arylmethanols to DNA

Biosynthesis of the regulatory oxysterol, 5-cholesten-3β,25-diol 3-sulfate, in hepatocytes

“…Furthermore, Fuda et al (21) and Javitt et al (22) reported that hydroxycholesterol sulfotransferase 2B1b (SULT2B1b) effectively sulfates a variety of oxysterols. Three SULT isoenzymes in human and four in rat were recently cloned and identified (19,(22)(23)(24). He, Frost, and Falany (25) reported that SULT2B1b has been localized to the cytosol and nuclei of both human cells and tissues.…”

Sulfation through the looking glass—recent advances in sulfotransferase research for the curious

“…For example, to date human is the only species in which a catecholamine-specific SULT isoform (SULT1A3) has been identified, consistent with the high circulating levels of catecholamine sulfates found in humans and other primates. 3,4 Rodents have multiple isoforms of the hydroxysteroid SULT subfamily 2A, [5][6][7] whereas so far only a single SULT2A enzyme has been identified and characterised in humans. 8 Also, it is now clear that SULTs are abundantly expressed in the human fetus [9][10][11][12][13] -other 'drug metabolising enzymes' such as the cytochromes P450 (CYPs), UDPglucuronosyltransferases (UGTs) etc are, in general not expressed at significant levels until after birth 14,15 -thus SULTs may represent a front line of chemical defence in the developing human.…”

Regulation of Rat Hepatic Hydroxysteroid Sulfotransferase (SULT2-40/41) Gene Expression by Glucocorticoids: Evidence for a Dual Mechanism of Transcriptional Control

“…It stands to reason that disruption or deregulation of SULT2 gene expression may have serious consequences for hepatic cholestasis, xenobiotic detoxication, and hormone response mechanisms. Although the deduced amino acid sequences corresponding to individual SULT2 isoforms maintain a close (ϳ86.3 to 99.6%) structural identity (Watabe et al, 1994;Yamazoe et al, 1994;Runge-Morris et al, 1998), we and others have shown that the mRNA expression of separate SULT2 isoforms is differentially regulated in response to hormone or xenobiotic treatment. For example, noncoordinate regulation by growth hormone of the rat hepatic SULT2-40/41 and SULT2-20/21 isoforms in growth hormone-deficient rats has been previously described (Ueda et al, 1997).…”

“…Depending on the stability of the sulfate ester that is formed, SULT2-catalyzed reactions may culminate in the creation of a polar end product that is amenable to excretion and elimination (detoxication) or in the bioactivation of a procarcinogen to a highly reactive intermediate. Moreover, because sulfated hormones are generally considered to be receptor inactive, alterations in SULT2 gene expression have the potential to shift the balance of intratissue active hormone levels and affect gene expression.In a broad-based search for hepatic genes that undergo altered expression during aging, Roy and coworkers cloned two rat senescence marker protein genes, SMP2A and SMP2B (Song et al, 1990), that were later identified as sulfotransferase genes of the SULT2 family (Ogura et al, 1990a;Watabe et al, 1994). Age-and gender-related expression of the rat hepatic SULT2 gene family has long been recognized as a key feature of these enzymes and strongly suggests that hormonal regulation is central to SULT2 gene expression.…”

“…In a broad-based search for hepatic genes that undergo altered expression during aging, Roy and coworkers cloned two rat senescence marker protein genes, SMP2A and SMP2B (Song et al, 1990), that were later identified as sulfotransferase genes of the SULT2 family (Ogura et al, 1990a;Watabe et al, 1994). Age-and gender-related expression of the rat hepatic SULT2 gene family has long been recognized as a key feature of these enzymes and strongly suggests that hormonal regulation is central to SULT2 gene expression.…”