Localization of type 1 17 beta-hydroxysteroid dehydrogenase mRNA and protein in syncytiotrophoblasts and invasive cytotrophoblasts in the human term villi

The 17 beta-hydroxysteroid dehydrogenases (17 beta-HSDs) play a key role in the synthesis of sex steroids. The hallmark of this family of enzymes is t he interconversion, through their oxydoreductive reactivity at position C17 , of 17-keto- and 17 beta-hydroxy-steroids. Because this reaction essential ly transforms steroids having low binding activity for the steroid receptor to their more potent 17 beta-hydroxysteroids isoforms, it is crucial to th e control of the physiological activities of both estrogens and androgens. The human placenta produces large amounts of progesterone and estrogens thr oughout pregnancy. The placental type 1 17 beta-HSD enzyme (E17 beta-HSD) c atalyzes the reduction of the low activity estrogen, estrone, into the pote nt estrogen, estradiol. We studied the cell-specific expression of type 1 1 7 beta-HSD in human term placental villous tissue by combining in situ hybr idization to localize type 1 17 beta-HSD mRNA with immunohistochemistry usi ng an antibody against human placental lactogen, a trophoblast marker. Immu nolocalization of E17 beta-HSD was also performed. To ascertain whether oth er steroidogenic enzymes are present in the same cell type, cyto-chrome P45 0 cholesterol side-chain cleavage (P150scc), P450 aromatase, and type 1 3 b eta-hydroxysteroid dehydrogenase (3 beta-HSD) were also localized by immuno staining. Our results showed that the syncytium is the major steroidogenic unit of the fetal term villi. In fact, type 1 17 beta-HSD mRNA and protein, as well as P150scc, P450 aromatase, and SP-HSD immunoreactivities were fou nd in these cells. In addition, our results revealed undoubtedly that extra villous cytotrophoblasts (CTBs), e.g. those from which cell columns of anch oring villous originate, also express the type 1 17 beta-HSD gene. However, CTBs lying beneath the syncytial layer, e.g. those from which syncytiotrop hoblasts develop, contained barely detectable amounts of type 1 17 beta-HSD mRNA as determined by in situ hybridization. These findings, along with th ose from other laboratories confirm the primordial role of the syncytium in the synthesis of steroids during pregnancy. In addition, our results indic ate for the first time that CTBs differentiating along the invasive pathway contain type 1 17 beta-HSD mRNA.