GENE-EXPRESSION OF 17-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-2 ISOZYME IN PRIMARY CULTURES OF HUMAN TROPHOBLASTS PREDICTS DIFFERENT MECHANISMS REGULATING TYPE-1 AND TYPE-2 ENZYMES

Two 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) genes, types 1 and 2, have been cloned. The two isozymes show a 30% sequence homology but differ markedly in their kinetic properties. To date, the steroid ogenic capacity of the placenta has been associated with syncytium for mation. In this study, we have investigated 17 beta-HSD type 1 and typ e 2 gene expression during trophoblast differentiation in culture. We observed that term placenta and fetal cotyledons contain large amounts of both messenger RNAs (mRNAs). In culture, the type 1 gene is expres sed concurrent with syncytium formation. However, type 2 expression is barely detectable in freshly isolated cytotrophoblasts and undetectab le in syncytiotrophoblasts. Incubation of trophoblasts with progestero ne and estradiol increased type 1 mRNA but did not restore 17 beta-HSD type 2 expression. 17 beta-HSD activities with substrates that differ entiate the type 1 and type 2 enzymes correlated with the gene express ion results. Type 1 activity decreased in freshly isolated trophoblast s by 2-fold and remained at these levels throughout the culture period . However, when compared with levels measured in term microsomes, type 2 activity decreased by 20-fold in freshly isolated cells and decreas ed again in culture by 5-fold. The expression pattern of 17 beta-HSD t ype 1 and type 2 activity in trophoblasts in culture suggests differin g mechanisms regulate type 1 and type 2 mRNA levels.