Differential Expression and Activity of 11β-Hydroxysteroid Dehydrogenase in Human Placenta and Fetal Membranes from Pregnancies with Intrauterine Growth Restriction

Abstract

Objectives: To study the expression and the function of the 11β-hydroxysteroid dehydrogenase enzyme 1 (11β-HSD1) and 2 (11β-HSD2) in placenta and the fetal membranes from pregnancies with intrauterine growth restriction (IUGR) and from controls. Methods: Amnion, chorion, decidua and cotyledon were separated from placenta; mRNA was analyzed by TaqMan real-time technology and proteins by Western blot; enzyme activities were measured by the conversion of ³H-cortisol to ³H-cortisone and vice versa. Results: Predominant mRNA expression (p < 0.001) was found for 11β-HSD1 in chorion and for 11β-HSD2 in decidua and cotyledon. In pregnancies with IUGR, 11β-HSD1 was upregulated in chorion (mean ΔCt 11β-HSD:18S mRNA 193.5 vs. 103.0 in controls respectively, p < 0.05) and 11β-HSD2 was downregulated in decidua (mean ΔCt 11β-HSD2:18S mRNA 0.18 vs. 15.88 in controls respectively, p < 0.05). 11β-HSD1 protein levels were reduced in amnion and 11β-HSD1 and 11β-HSD2 oxidase activity in decidua and cotyledon were reduced from pregnancies with IUGR. Conclusion: Reduced synthesis or activity of 11β-HSD1 or 2 in cases of IUGR is shown in some but not in all tissues. The local mRNA expression of 11β-HSD1 in chorion may reflect a mechanism on the post-transcriptional gene regulation to stimulate the formation of cortisone in IUGR. To provoke increasing activity with oxidase stimulators could be a future therapy in cases of IUGR.