STEROID SULFATION BY EXPRESSED HUMAN CYTOSOLIC SULFOTRANSFERASES

The human cytosolic sulfotransferases (STs), dehydroepiandrosterone su lfotransferase (DHEA-ST) and the phenol-sulfating form of phenol sulfo transferase, (P-PST), have been expressed in bacteria and used to inve stigate the ability of the cloned enzymes to conjugate steroids and re lated compounds. DHEA-ST was capable of sulfating all of the 3-hydroxy steroids, testosterone and estrogens tested as substrates. The 3-hydro xysteroids, androsterone, epiandrosterone and androstenediol, were con jugated at 50-60% of the rate of DHEA. Of the steroids tested, P-PST w as capable of conjugating only the estrogens. The catechol estrogens, 2-hydroxyestradiol, 4-hydroxyestradiol and 4-hydroxyestrone, and compo unds with estrogenic activity such as 17 alpha-ethynylestradiol and tr ans-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 t he expressed human STs are valuable in analyzing the overlapping subst rate specificities of these enzymes and that P-PST may have an importa nt role in the metabolism of estrogens and estrogenic compounds in hum an tissues.