11β-hydroxysteroid dehydrogenase expression in first trimester human trophoblasts

This study evaluated the levels and the enzymatic characteristics of 11β-hydroxysteroid dehydrogenase activity (11β-HSD) of chorionic villi isolated from first trimester human placenta. The results demonstrated a predominant expression of the NAD-dependent dehydrogenase isoform (11β-HSD2) over the NADP-dependent oxoreductase (11Iβ-HSD1). Thus, in tissue homogenates exogenous NAD increased the conversion of corticosterone to 11-dehydrocorticosterone of about 14-fold while NADP was ineffective. There was no conversion of 11-dehydrocorticosterone to corticosterone either with NADH or NADPH demonstrating the lack of reductase activity. In keeping with these results, RT-PCR analysis indicated a mRNA for 11β-HSD2 in villous tissue while 11β-HSD1 mRNA levels were undetectable. In addition, immunohistochemical staining localized the 11β-HSD2 protein to syncytiotrophoblasts and cell columns of the chorionic villi. These results suggest roles for the trophoblast-associated 11β-HSD2 oxidative activity in modulating the exposure of the embryo to active glucocorticoids in the early gestation and in regulating trophoblasts invasion of the uterine wall.