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 steroi dogenic enzyme that catalyzes the reversible interconversion of estron e and estradiol. In this study, we investigated the roles of epidermal growth factor (EGF) and tumor growth factor-alpha TGF alpha) in the r egulation of 17HSD type 1 gene expression and catalytic activity in cu ltured JAR, JEG-3, and BeWo choriocarcinoma cells. EGF and TGF alpha i ncreased 17HSD type 1 protein concentrations in JAR and JEG-3 cells, a s measured by time-resolved immunofluorometric assay, and 17HSD cataly tic activity, as determined by production of estradiol from estrone. T hese increases were accompanied by parallel increases in concentration s of the 1.3-kilobase messenger RNA coding for 17HSD type 1 in these c ells. EGF receptor tyrosine kinase activity inhibitors, tyrphostins, i nhibited EGF action in JEG-3 cells, indicating that tyrosine kinase ac tivity is needed for stimulation of the 17HSD type 1 gene. Treatment w ith 8-bromo-cAMP or phorbol 12-myristate 13-acetate increased the amou nt of 17HSD type 1 protein. Furthermore, phorbol 12-myristate 13-aceta te potentiated the stimulatory effect of EGF. These results suggest th at EGF and/or TGF alpha may play an important role in 17HSD type 1 reg ulation and, consequently, in estrogen production in the human placent a.