Steroid sulfation by expressed human cytosolic sulfotransferases.
The human cytosolic sulfotransferases (STs), dehydroepiandrosterone sulfotransferase (DHEA-ST) and the phenol-sulfating form of phenol sulfotransferase, (P-PST), have been expressed in bacteria and used to investigate the ability of the cloned enzymes to conjugate steroids and related compounds. DHEA-ST was capable of sulfating all of the 3-hydroxysteroids, testosterone and estrogens tested as substrates. The 3-hydroxysteroids, androsterone, epiandrosterone and androstenediol, were conjugated at 50-60% of the rate of DHEA. Of the steroids tested, P-PST was capable of conjugating only the estrogens. The catechol estrogens, 2-hydroxyestradiol, 4-hydroxyestradiol and 4-hydroxyestrone, and compounds with estrogenic activity such as 17 alpha-ethynyl-estradiol and trans-4-hydroxytamoxifen, were also tested as substrates. DHEA-ST showed little or no sulfation activity with these compounds; however, all of these compounds were sulfated by P-PST. These results indicate that the expressed human STs are valuable in analyzing the overlapping substrate specificities of these enzymes and that P-PST may have an important role in the metabolism of estrogens and estrogenic compounds in human tissues.
Falany
C N
CN
Department of Pharmacology, University of Alabama at Birmingham 35294.
Wheeler
J
J
Oh
T S
TS
Falany
J L
JL
D000595:Amino Acid Sequence; D015114:Androstenediol / Q000378:metabolism; D000738:Androsterone / Q000378:metabolism; D015239:Arylsulfotransferase / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D003600:Cytosol / Q000201:enzymology; D004926:Escherichia coli / Q000235:genetics; D004967:Estrogens / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*; D013379:Substrate Specificity; D013431:Sulfates / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism
D004967:Estrogens; D011994:Recombinant Proteins; D013256:Steroids; D013431:Sulfates; D013739:Testosterone; D015114:Androstenediol; D000738:Androsterone; D015238:Sulfotransferases; C019998:dehydroepiandrosterone sulfotransferase; D015239:Arylsulfotransferase