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 [hydroxysteroid] 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 .mu.M) and danazol (Ki = 0.6 .mu.M); anabolic steroids and norethisterone were weaker inhibitors. Of the non-steroids tested only diethylstilbestrol and o-demethyl CI-680 [3-[p-.alpha.-(p-methoxyphenyl)-.beta.-nitrostyryl]phenoxy)-N,N-dimethylpropylamine monocitrate] were inhibitors and they showed a greater affinity for soluble 17.beta.-HSD. Ki values for estradiol-17.beta. (0.8 .mu.M), progesterone (27.0 .mu.M) and 20.alpha.-dihydroprogesterone (1.5 .mu.M) 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.