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

Abstract

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 steroidogenic capacity of the placenta has been associated with syncytium formation. In this study, we have investigated 17 beta-HSD type 1 and type 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 expressed concurrent with syncytium formation. However, type 2 expression is barely detectable in freshly isolated cytotrophoblasts and undetectable in syncytiotrophoblasts. Incubation of trophoblasts with progesterone and estradiol increased type 1 mRNA but did not restore 17 beta-HSD type 2 expression. 17 beta-HSD activities with substrates that differentiate the type 1 and type 2 enzymes correlated with the gene expression results. Type 1 activity decreased in freshly isolated trophoblasts 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 decreased again in culture by 5-fold. The expression pattern of 17 beta-HSD type 1 and type 2 activity in trophoblasts in culture suggests differing mechanisms regulate type 1 and type 2 mRNA levels.