Enhancement of cortisol-induced 11beta-hydroxysteroid dehydrogenase type 1 expression by interleukin 1beta in cultured human chorionic trophoblast cells

Endocrinology. 2006 May;147(5):2490-5. doi: 10.1210/en.2005-1626. Epub 2006 Feb 9.


Chorion is the most abundant site of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) expression within intrauterine tissues. It is important to study the regulation of 11beta-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 mum) and IL-1beta (10 ng/ml) for 24 h significantly increased 11beta-HSD1 mRNA expression and reductase activity in cultured human chorionic trophoblasts. A further significant increase of 11beta-HSD1 mRNA expression and reductase activity was observed with cotreatment of cortisol and IL-1beta. To explore the mechanism of induction, 11beta-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 microM) or IL-1beta (10 ng/ml) significantly increased reporter gene expression. Likewise, an additional increase in reporter gene expression was observed with cotreatment of cortisol and IL-beta. To explore the physiological significance of 11beta-HSD1 induction in the chorion, we studied the effect of cortisol on cytosolic phospholipase A(2) and cyclooxygenase 2 expression. We found that treatment of chorionic trophoblast cells with cortisol (1 microM) induced both cytosolic phospholipase A(2) and cyclooxygenase 2 mRNA expression. We conclude that cortisol up-regulates 11beta-HSD1 expression through induction of promoter activity, and the effect was enhanced by IL-1beta, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / biosynthesis*
  • Cell Line
  • Chorion / metabolism
  • Cloning, Molecular
  • Cyclooxygenase 2 / biosynthesis
  • Cytokines / metabolism
  • Cytosol / metabolism
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation
  • Genes, Reporter
  • Genetic Vectors
  • Humans
  • Hydrocortisone / metabolism*
  • Interleukin-1 / metabolism*
  • Luciferases / metabolism
  • Phospholipases A / metabolism
  • Plasmids / metabolism
  • Promoter Regions, Genetic
  • RNA / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Trophoblasts / metabolism*


  • Cytokines
  • Interleukin-1
  • RNA, Messenger
  • RNA
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Luciferases
  • Cyclooxygenase 2
  • Phospholipases A
  • Hydrocortisone