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

Abstract

Hepatocyte nuclear factor 1α (HNF-1α) is a homeodomain-containing transcription factor and is important in postnatal growth and development in mice. In the HNF-1α-deficient liver, the expressions of a large set of growth hormone (GH)-responsive genes were significantly downregulated. By analyzing various HNF-1α mutant mice, we disclosed a mechanism by which hepatic HNF-1α regulates the expression of GH-responsive genes that are crucial for growth and development. We found that HNF-1α 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-1α 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.