DIFFERENTIAL ESTROGEN SUBSTRATE SPECIFICITIES FOR TRANSIENTLY EXPRESSED HUMAN PLACENTAL 17-BETA-HYDROXYSTEROID DEHYDROGENASE AND AN ENDOGENOUS ENZYME EXPRESSED IN CULTURED COS-M6 CELLS

The metabolism of estrogens catalyzed by human placental 17beta-hydrox ysteroid dehydrogenase (17HSD) transiently expressed in COS-m6 cells w as studied, and the properties of the enzyme were compared with those of an endogenous hydroxysteroid dehydrogenase (HSD) expressed in the c ells. In cultured cells, the endogenous HSD had almost exclusively oxi dative activity, converting estradiol to estrone (oxidative and reduct ive activity, 0.84 +/- 0.164 and 0.034 +/- 0.01 nmol/mg protein . h, r espectively). This was, nevertheless, opposed to the activity of the t ransiently expressed human placental 17HSD, as a high reductive activi ty (0.86 +/- 0.30 nmol/mg protein . h) appeared in the cells after tra nsfection, whereas oxidative activity was not significantly induced. I n the different transfections, the reductive activity was induced 13- to 34-fold, and the oxidative activity in the 17HSD-transfected cells was 65-162% of that in the mock-transfected cells. Thus, in cultured c ells, these two enzymes preferentially catalyze opposite reactions. Wh en the metabolism of the estrogens was followed up to 20 h, the two en zymes were found to regulate the proportion of estrone to estradiol in the culture medium. The different properties found for the enzymes sh ow that the endogenous HSD expressed in the COS-m6 cells is an additio nal member of the family of 17HSD enzymes. It is suggested that differ ent 17HSD enzymes exist, with differential estrogen substrate specific ities in cultured cells. Thus, in addition to cofactor and substrate a vailability, the biological activity of estrogens in different cell ty pes may be regulated by the expression of different forms of 17HSD enz ymes, resulting in the dominance of either estradiol or estrone produc tion.