DIFFERENTIAL EXPRESSION OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1 AND TYPE-2 IN HUMAN PLACENTA AND FETAL MEMBRANES

Two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) are present in mammals. 11 beta HSD1 interconverts biologically active co rtisol and inactive cortisone, whereas 11 beta HSD2 only converts cort isol to cortisone. Placental 11 beta HSD has been proposed to protect the fetus from high level of maternal glucocorticoids. Although bidire ctional activity of 11 beta HSD has been demonstrated in homogenized h uman placental tissues, the tissue and cellular distribution of 11 bet a HSD1 has not been resolved. In this study, the cellular localization of 11 beta HSD1 protein and levels of its messenger ribonucleic acid (mRNA) in human placenta and fetal membranes were determined by immuno histochemistry and Northern blot analysis, respectively. We found that 11 beta HSD1 immunoreactivity was present in the placental extravillo us intermediated trophoblasts, chorion trophoblasts, amnion epithelial cells, and stromal cells of the decidua vera. Positive staining was a lso observed in the endothelium of the blood vessels in both placental villous tissue and umbilical cord. However, in contrast to previous r eports of immunoreactive 11 beta HSD2 localization, 11 beta HSD1 immun oreactivity was undetectable in placental syncytiotrophoblast. Using a human 11 beta HSD1 complementary DNA as probe, a 1.5-kilobase mRNA tr anscript was detected in the chorion, amnion, and placental tissue, wi th the greatest amount in the chorion. In contrast, the 1.9-kilobase m RNA of 11 beta HSD2 was observed only in the placenta, not in the chor ion and amnion. The process of labor had no significant effect on leve ls of 11 beta HSD1 or 11 beta HSD2 mRNA in the chorion or placenta. We conclude that there is a striking difference in the tissue localizati on of 11 beta HSD1 and 11 beta HSD2 expression in the late gestation h uman placenta and fetal membranes, which may discretely determine the accessibility of bioactive glucocorticoid to specific cell types.