Inhibition of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activities of human placenta by steroids and non-steroidal hormone agonists and antagonists.

Various naturally occurring steroids, synthetic steroid derivatives and non-steroidal hormone agonists and antagonists were assayed as inhibitors of human placental 17 beta-HSD activities. Microsomal 17 beta-HSD was inhibited by C18-, C19- and C21-steroids. Soluble 17 beta-HSD was highly specific for C18-steroids. In contrast to the soluble activity, the microsomal enzyme also had a strong affinity for ethinylestradiol (KI = 0.3 microM) and danazol (KI = 0.6 microM); anabolic steroids and norethisterone were weaker inhibitors. Of the non-steroids tested only diethylstilbestrol and o-demethyl CI-680 were inhibitors and they showed a greater affinity for soluble 17 beta-HSD. KI-values for estradiol-17 beta, (0.8 microM), progesterone (27.0 microM) and 20 alpha-dihydroprogesterone (1.5 microM) were comparable to reported tissue levels of these compounds, consistent with a possible competition in vivo among naturally occurring C18-, C19-, and C21-steroids for the active site of microsomal 17 beta-HSD.