Enzymatic sulfation of steroids. XV. Studies differentiating between rat liver androgen, estrogen, bile acid, glucocorticoid and phenol sulfotransferases

Abstract

Earlier reports left the number of enzymes that catalyzed phenol, androgen, estrogen, bile acid and glucocorticoid sulfation obscure. Here, we have utilized chromatographic, immunochemical and endocrinologic methods to compare and differentiate these enzymes in rat liver. Sulfotransferases I, II, and III--which sulfate glucocorticoids--were used in this comparison. We found that phenols were sulfated by phenol sulfotransferases 1 and 2, which were unrelated to the other enzymes studied here. Large amounts of phenol sulfotransferase 1 were found in both sexes. Large amounts of phenol sulfotransferase 2 were restricted to males. By contrast, the small amount of androgen sulfation found in both sexes appeared to be mediated by sulfotransferase II, which preferred 3 beta-hydroxysteroids, but also sulfated estrogens and glucocorticoids to lesser extents. The sulfation of estrogens presented a more complex picture. Most estradiol sulfotransferase activity in both sexes was due to an enzyme that sulfated estrone poorly, and did not sulfate the other steroids tested. This specific estradiol sulfotransferase was unrelated to the other sulfotransferases described here. Smaller amounts of estrogen sulfotransferase activity that sulfated estradiol and estrone equally well were present at concentrations dependent on the sex of test animals. This enzyme activity appeared to be due to sulfotransferases I, II and III. Most bile acid sulfotransferase activity eluted from DEAE-Sephadex A-50 columns with sulfotransferases I and II. However, data with males suggested that these enzymes were not responsible. Thus, phenols, androgens, estrogens and glucocorticoids were sulfated by six enzymes of differing substrate specificity: phenol sulfotransferases 1 and 2, specific estradiol sulfotransferase, and sulfotransferases I, II, and III. Unique bile acid sulfotransferases also appeared probable.