Disease relevance of SULT2A1

• MCF-7 human mammary carcinoma cells have been reported to possess beta-estradiol and dehydroepiandrosterone sulfotransferase activities [1].
• Association of SULT2A1 allelic variants with plasma adrenal androgens and prostate cancer in African American men [2].
• We expressed rat hydroxysteroid sulfotransferase a, a liver-specific enzyme, and corresponding human sulfotransferase in bacteria (Salmonella typhimurium) and in a mammalian cell line (Chinese hamster V79 cells) and tested alpha-hydroxytamoxifen for DNA adduct formation and mutagenicity in these systems, using unmodified cells as controls [3].
• Role for enhanced faecal excretion of bile acid in hydroxysteroid sulfotransferase-mediated protection against lithocholic acid-induced liver toxicity [4].
• We have previously described a type of selective T cell deficiency (STD) characterized by persistent infections reminiscent of severe combined immunodeficiency [5].

Psychiatry related information on SULT2A1

• The enzyme in the adrenal responsible for synthesising DHEAS, hydroxysteroid sulphotransferase (HST), is therefore essential for human development [6].
• To fully exploit the reflex-testing capabilities and maximize the potential of the HST a computerized decision-making algorithm was developed [7].

High impact information on SULT2A1

• These reciprocal changes in mRNA concentrations in mutant females were reflected by an induction of a high affinity estrogen sulfotransferase activity and a concomitant loss of dehydroepiandrosterone sulfotransferase activity [8].
• We found that activation of PXR also increases the activity and gene expression of the phase II conjugating enzyme dehydroepiandrosterone sulfotransferase (STD) known to sulfate LCA to facilitate its elimination [9].
• DST has a broad range of substrate specificity and is responsible for the age- and sex-specific activation of certain polycyclic aromatic hepatocarcinogens as well, by converting them to electrophilic sulfonated derivatives [10].
• Androgen inactivation via sulfonation of the hormone by dehydroepiandrosterone sulfotransferase (DST), an androgen-repressible enzyme, also contributes to the age- and sex-dependent regulation of hepatic androgen sensitivity [10].
• The findings in this large study show a significant contribution to mortality among untreated early post-myocardial infarction survivors from transient STD on 24-hour monitoring [11].

Chemical compound and disease context of SULT2A1

• Dehydroepiandrosterone sulfotransferase as a possible shunt for the control of steroid metabolism in human mammary carcinoma [12].
• Expression of human estrogen sulfotransferase in Salmonella typhimurium: differences between hHST and hEST in the enantioselective activation of 1-hydroxyethylpyrene to a mutagen [13].
• Our results indicate that the active recombinant enzyme expressed in E. coli is a homodimer.Biochemical properties for purified DHEA-ST were studied using DHEA as a substrate [14].
• Recombinant human dehydroepiandrosterone sulfotransferase (DHEA-ST) expressed in glutathione sulfotransferase fusion form in E. coli was purified using glutathione sepharose 4B affinity adsorption chromatography, a Factor Xa cleavage step, and Q-sepharose fast flow column chromatography [14].
• The decreased expression of DHEA-ST may reflect autonomous neoplastic cortisol secretion and subsequent ACTH suppression in ASCA and adrenal Cushing's syndrome [15].

Biological context of SULT2A1

• About seven SF1 binding sites exist on the SULT2A1 gene [16].
• To identify and localize the critical SF1 binding site, series of deletion mutants of SULT2A1 promoter fragments in pGL2 plasmid were constructed [16].
• SULT2A1 and SF1 up-regulation at protein and RNA levels in thyroidectomized rats occurred after T(3) application [16].
• SULT2B1 mapped to human chromosome band 19q13.3, approximately 500 kb telomeric to the location of SULT2A1 [17].
• In contrast to the wide substrate specificity of SULT2A1, SULT2B1a and SULT2B1b specifically catalyzed the sulfonation of 3beta-hydroxysteroids with high catalytic efficiency [18].

Anatomical context of SULT2A1

• No expression of the hydroxysteroid sulphotransferase SULT2A1 was detected at any time in the endometrium [19].
• In contrast to the limited tissue distribution of SULT2A1, SULT2B1 was detected in a variety of hormone-responsive tissues including placenta, ovary, uterus, and prostate [18].
• Immunoblot analysis of several different human liver cytosol samples with the rabbit anti-human liver DHEA-ST antiserum detected only a single 35-kDa protein in each liver [20].
• The human hydroxysteroid sulfotransferase, dehydroepiandrosterone sulfotransferase (DHEA-ST), is highly expressed in liver and adrenal cortex and displays reactivity towards a broad range of hydroxysteroids including 3 beta-hydroxysteroids, 3 alpha-hydroxysteroids, estrogens with a 3-phenolic moiety, and 17-hydroxyl group of androgens [21].
• These results represent a step toward understanding the molecular basis for individual variation in the expression and function of EST and DHEA ST in the human small intestine [22].

Associations of SULT2A1 with chemical compounds

• Crystal structure of human cholesterol sulfotransferase (SULT2B1b) in the presence of pregnenolone and 3'-phosphoadenosine 5'-phosphate. Rationale for specificity differences between prototypical SULT2A1 and the SULT2BG1 isoforms [23].
• SULT2A1 is highly expressed in the adrenal where it is responsible for the sulfation of hydroxysteroids including conversion of dehydroepiandrosterone to dehydroepiandrosterone sulfate and in the liver where it is responsible for sulfation of bile acids and circulating hydroxysteroids [24].
• Taken together, the expression of ERRalpha in the adrenal and its regulation of SULT2A1 suggest an important role for this orphan receptor in the regulation of adrenal steroid production [25].
• Cycloheximide inhibited T(3)-induced SULT2A1 expression, suggesting that regulation was indirect [16].
• In the present study, we have investigated the hypothesis that OHPCBs interact with family 2 hydroxysteroid (alcohol) SULTs (e.g., human SULT2A1), enzymes that are physiologically important for the metabolic transformations of several key endogenous hydroxysteroids as well as xenobiotic alcohols [26].

Regulatory relationships of SULT2A1

• Human vitamin D receptor (hVDR) also upregulated hSULT2A1 gene expression while human pregnane X receptor (hPXR) downregulated it [27].
• The natural xanthones reversibly inhibited SULT1A1 with IC50 values ranging from 1.6 to 7 microM whereas much higher amounts of these compounds were required to inhibit SULT2A1 (IC50 values of 26-204 microM) [28].

Other interactions of SULT2A1

• The results of this study suggest that DHEA-ST is the major steroid ST present in human liver and adrenal tissue and that the physical, biochemical, and kinetic properties of adrenal DHEA-ST are similar if not identical to those of the liver form of the enzyme [20].
• SULT1E1 displayed the lowest Km (0.2 microM) for 4-OHT sulfation and SULT2A1 the lowest (0.3 microM) for raloxifene sulfation [29].
• Low activity with SULT1B1 was only seen at the highest concentration (100 microM) and no activity with SULT1C2 or SULT2A1 was observed [30].
• Both SF1 and GATA-6 were positive regulators of SULT2A1 promoter constructs [24].
• The thermal inactivation profile of E1 ST suggested that this activity might be related to both DHEA ST and TS PST [31].

Analytical, diagnostic and therapeutic context of SULT2A1

• DHEA-ST activity was purified from the 100,000 x g supernatant fraction of human adrenal tissue by DEAE-Sepharose CL-6B chromatography and 3',5'-diphosphoadenosine-agarose affinity chromatography [20].
• Polyclonal antibodies to human EST and DHEA ST were developed, and Western blot analysis demonstrated that the antibodies were specific [22].
• We set out to characterize immunochemically the nature and extent of individual variation in the expression of EST and DHEA ST in the human small intestine after Northern blot analysis had demonstrated that both enzymes were expressed in that tissue [22].
• In addition, the most common of the nonsynonymous cSNPs disrupted the portion of SULT2A1 involved with dimerization, and this variant allozyme behaved as a monomer rather than a dimer during gel filtration chromatography [32].
• Human liver dehydroepiandrosterone sulfotransferase: molecular cloning and expression of cDNA [33].

References