Regulation of 17 beta-hydroxysteroid dehydrogenase type 1 by epidermal growth factor and transforming growth factor-alpha in choriocarcinoma cells.
17 beta-Hydroxysteroid dehydrogenase type 1 (17HSD type 1) is a steroidogenic enzyme that catalyzes the reversible interconversion of estrone and estradiol. In this study, we investigated the roles of epidermal growth factor (EGF) and tumor growth factor-alpha (TGF alpha) in the regulation of 17HSD type 1 gene expression and catalytic activity in cultured JAR, JEG-3, and BeWo choriocarcinoma cells. EGF and TGF alpha increased 17HSD type 1 protein concentrations in JAR and JEG-3 cells, as measured by time-resolved immunofluorometric assay, and 17HSD catalytic activity, as determined by production of estradiol from estrone. These increases were accompanied by parallel increases in concentrations of the 1.3-kilobase messenger RNA coding for 17HSD type 1 in these cells. EGF receptor tyrosine kinase activity inhibitors, tyrphostins, inhibited EGF action in JEG-3 cells, indicating that tyrosine kinase activity is needed for stimulation of the 17HSD type 1 gene. Treatment with 8-bromo-cAMP or phorbol 12-myristate 13-acetate increased the amount of 17HSD type 1 protein. Furthermore, phorbol 12-myristate 13-acetate potentiated the stimulatory effect of EGF. These results suggest that EGF and/or TGF alpha may play an important role in 17HSD type 1 regulation and, consequently, in estrogen production in the human placenta.
Lewintre
E J
EJ
Biocenter, University of Oulu, Finland.
Orava
M
M
Vihko
R
R
D015067:17-Hydroxysteroid Dehydrogenases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D002822:Choriocarcinoma / Q000201:enzymology* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D009570:Nitriles / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D020032:Tyrphostins
D002396:Catechols; D009570:Nitriles; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D020032:Tyrphostins; C060152:tyrphostin 47; D015124:8-Bromo Cyclic Adenosine Monophosphate; D004815:Epidermal Growth Factor; D015067:17-Hydroxysteroid Dehydrogenases; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate