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Enhancement of Cortisol-Induced 11ß-Hydroxysteroid dehydrogenase Type 1 Expression by Interleukin 1ß in Cultured Human Chorionic Trophoblast Cells

School of Life Sciences, The First Maternal and Fetal Care Hospital, Fudan University (W.L., Y.W., T.D., K.S.), and Second Military Medical University (L.G.), Shanghai 200433, China; and Department of Obstetrics and Gynecology (L.M.), College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267

Address all correspondence and requests for reprints to: Dr. Kang Sun, Department of Physiology and Biophysics, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, People’s Republic of China. E-mail: sunkang2000{at}yahoo.com.

Chorion is the most abundant site of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) expression within intrauterine tissues. It is important to study the regulation of 11ß-HSD1 expression in the chorion in terms of local cortisol production during pregnancy. Using real-time PCR and enzyme activity assay, we found that cortisol (1 µM) and IL-1ß (10 ng/ml) for 24 h significantly increased 11ß-HSD1 mRNA expression and reductase activity in cultured human chorionic trophoblasts. A further significant increase of 11ß-HSD1 mRNA expression and reductase activity was observed with cotreatment of cortisol and IL-1ß. To explore the mechanism of induction, 11ß-HSD1 promoter was cloned into pGL3 plasmid expressing a luciferase reporter gene. By transfecting the constructed vector into WISH cells, an amnion-derived cell line, we found that cortisol (1 µM) or IL-1ß (10 ng/ml) significantly increased reporter gene expression. Likewise, an additional increase in reporter gene expression was observed with cotreatment of cortisol and IL-ß. To explore the physiological significance of 11ß-HSD1 induction in the chorion, we studied the effect of cortisol on cytosolic phospholipase A₂ and cyclooxygenase 2 expression. We found that treatment of chorionic trophoblast cells with cortisol (1 µM) induced both cytosolic phospholipase A₂ and cyclooxygenase 2 mRNA expression. We conclude that cortisol up-regulates 11ß-HSD1 expression through induction of promoter activity, and the effect was enhanced by IL-1ß, suggesting that more biologically active glucocorticoids could be generated in the fetal membranes in the presence of infection, which may consequently feed forward in up-regulation of prostaglandin synthesis.

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