Role of glucocorticoid receptor and CCAAT/enhancer-binding protein α in the feed-forward induction of 11β-hydroxysteroid dehydrogenase type 1 expression by cortisol in human amnion fibroblasts

• DOI: 10.1677/joe-07-0303
• Publication Date: 2007-10-19T18:39:10Z
• Authors: Zhen Yang; Chunming Guo; Ping Zhu; Wenjiao Li; Leslie Myatt; Kang Sun
• Keywords: Ccaat-enhancer-binding proteins; Amnion; Response element

The amount of cortisol available to its receptors is increased by the pre-receptor enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) which converts cortisone cortisol. We examined molecular mechanisms feedback effect on 11beta-HSD1 mRNA expression in human amnion fibroblasts. Our data showed that cortisol-induced dose dependently fibroblasts, could be completely blocked both transcription inhibitor 5,6-dichlorobenzimidazole riboside and glucocorticoid receptor (GR) antagonist RU486, partially global inhibition CCAAT/enhancer-binding proteins (C/EBPs) with transfection C/EBP-specific dominant-negative CMV500 plasmid (AC/EBP) into cells. Likewise, induction promoter activity also RU486 AC/EBP transfection. Progressive 5' deletion 11beta-HSD1promoter located region responsible for cortisol's within -204 bp upstream start site. Specific nucleotide mutations putative responsive element or CCAAT this attenuated Moreover, chromatin immunoprecipitation assay electrophoretic mobility shift GR C/EBPalpha but not C/EBPbeta bind upon stimulation In conclusion, we demonstrated were involved via binding may cast a feed-forward production fetal membranes at end gestation.