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HORMONES AND SIGNALING

Hepatocyte nuclear factor-1 regulates glucocorticoid receptor expression to control postnatal body growth

Laboratory of Molecular Pathology, Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan

Submitted 17 February 2008 ; accepted in final form 19 June 2008

Hepatocyte nuclear factor 1 (HNF-1) is a homeodomain-containing transcription factor and is important in postnatal growth and development in mice. In the HNF-1-deficient liver, the expressions of a large set of growth hormone (GH)-responsive genes were significantly downregulated. By analyzing various HNF-1 mutant mice, we disclosed a mechanism by which hepatic HNF-1 regulates the expression of GH-responsive genes that are crucial for growth and development. We found that HNF-1 is required for the normal expression of glucocorticoid receptor (GR) specifically in livers. In the liver, GR, together with STAT5, is known to mediate the GH action by transactivating the GH-responsive genes that function in body growth and development. We further demonstrated that HNF-1 modulated GR gene expression by directly transactivating the GR gene promoter via a cryptic regulatory element located 3 bp upstream of the translation start site in exon 2 of the GR gene locus.

transactivation; promoter element