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Differential Expression of 11ß-Hydroxysteroid Dehydrogenase Types 1 and 2 in Human Placenta and Fetal Membranes¹

Medical Research Council Group in Fetal and Neonatal Health and Development, Departments of Physiology and Obstetrics and Gynecology, University of Toronto, Toronto; and the Departments of Obstetrics and Gynecology and Physiology, Lawson Research Institute, University of Western Ontario (K.Y.), Ontario, Canada

Address all correspondence and requests for reprints to: Dr. Kang Sun, Department of Physiology, Third Floor, Medical Science Building, Unversity of Toronto, 1 King’s College Circle, Toronto, Ontario, Canada M5S 1A8.

Two isoforms of 11ß-hydroxysteroid dehydrogenase (11ßHSD) are present in mammals. 11ßHSD1 interconverts biologically active cortisol and inactive cortisone, whereas 11ßHSD2 only converts cortisol to cortisone. Placental 11ßHSD has been proposed to protect the fetus from high level of maternal glucocorticoids. Although bidirectional activity of 11ßHSD has been demonstrated in homogenized human placental tissues, the tissue and cellular distribution of 11ßHSD1 has not been resolved. In this study, the cellular localization of 11ßHSD1 protein and levels of its messenger ribonucleic acid (mRNA) in human placenta and fetal membranes were determined by immunohistochemistry and Northern blot analysis, respectively. We found that 11ßHSD1 immunoreactivity was present in the placental extravillous intermediate trophoblasts, chorion trophoblasts, amnion epithelial cells, and stromal cells of the decidua vera. Positive staining was also observed in the endothelium of the blood vessels in both placental villous tissue and umbilical cord. However, in contrast to previous reports of immunoreactive 11ßHSD2 localization, 11ßHSD1 immunoreactivity was undetectable in placental syncytiotrophoblast. Using a human 11ßHSD1 complementary DNA as probe, a 1.5-kilobase mRNA transcript was detected in the chorion, amnion, and placental tissue, with the greatest amount in the chorion. In contrast, the 1.9-kilobase mRNA of 11ßHSD2 was observed only in the placenta, not in the chorion and amnion. The process of labor had no significant effect on levels of 11ßHSD1 or 11ßHSD2 mRNA in the chorion or placenta. We conclude that there is a striking difference in the tissue localization of 11ßHSD1 and 11ßHSD2 expression in the late gestation human placenta and fetal membranes, which may discretely determine the accessibility of bioactive glucocorticoid to specific cell types.

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