C/EBP Regulates Hepatic Transcription of 11β-Hydroxysteroid Dehydrogenase Type 1

Glucocorticoid action within individual cells is potently modulated by 11β-hydroxysteroid dehydrogenase (11β-HSD), which, by interconverting active and inert glucocorticoids, determines steroid access to receptors. Type 1 11β-HSD (11β-HSD1) is highly expressed in liver where it regenerates glucocorticoids, thus amplifying their action and contributing to induction of glucocorticoid-responsive genes, most of which are also regulated by members of the C/EBP (CAAT/enhancer-binding protein) family of transcription factors. Here we demonstrate that C/EBPα is a potent activator of the 11β-HSD1 gene in hepatoma cells and that mice deficient in C/EBPα have reduced hepatic 11β-HSD1expression. In contrast, C/EBPβ is a relatively weak activator of 11β-HSD1 transcription in hepatoma cells and attenuates C/EBPα induction, and mice that lack C/EBPβ have increased hepatic 11β-HSD1 mRNA. The 11β-HSD1promoter (between −812 and +76) contains 10 C/EBP binding sites, and mutation of the promoter proximal sites decreases the C/EBP inducibility of the promoter. One site encompasses the transcription start, and both C/EBPα and C/EBPβ are present in complexes formed by liver nuclear proteins at this site. The regulation of 11β-HSD1 expression, and hence intracellular glucocorticoid levels, by members of the C/EBP family provides a novel mechanism for cross-talk between the C/EBP family of transcription factors and the glucocorticoid signaling pathway.

• Publication year

  2000

• Venue

  Journal of Biological Chemistry

• Publication date

  2000-09-29

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M001286200
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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