Regulation of aromatase cytochrome P-450 and 17 beta-hydroxysteroid dehydrogenase messenger ribonucleic acid levels in choriocarcinoma cells.

摘要: In human placenta the enzyme complex aromatase catalyzes conversion of androgens to estrogens and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) mediates reversible interconversion of, e.g. estrone estradiol. We studied effects cholera toxin (CT), an activator adenylate cyclase, 12-O-tetradecanoyl phorbol 13-acetate (TPA), a ester protein kinase C activator, on levels messenger (m) RNAs encoding cytochome P-450 (P-450AROM) beta-HSD in cultured JEG-3 choriocarcinoma cells. With use oligonucleotide probes designed according known complementary DNA sequences, hybridizable mRNA transcripts 3.0, 2.4, 1.6 kilobases for P-450AROM were found Northern blot analysis cell RNA. A single 1.4-kilobase transcript was detected beta-HSD. Time-dependent increases cells observed both CT TPA with maximal at 24-48 h. increased concentration-dependent manner. The effects, about 4.8-fold 3.3-fold stimulations above basal levels, obtained 10 ng/ml 100 TPA, respectively. additive. induced time- manner its effect 10.1-fold within similar time concentration-dependence as mRNA. itself had no clear but it approximately doubled expression. Inhibition synthesis by cycloheximide decreased basal, stimulated expression This result is consistent hypothesis that induction gene mediated labile regulator resembling most other steroidogenic enzymes, whereas non-P450 appears be controlled different present results suggest that: 1) may least partly responsible our previously reported rate cells; 2) mainly through cAMP-dependent mechanism contrast multifactorial control mRNA; 3) inhibition has opposite these two key enzymes placental estrogen metabolism.