Submitted on February 17, 2008
Accepted on June 19, 2008
Hepatocyte Nuclear Factor-1
Regulates Glucocorticoid Receptor Expression to Control Postnatal Body Growth
Wan-Yi Lin1, Yu-Jie Hu1, and Ying-Hue Lee2*
1 Inst. Mol. Biol., Academia Sinica, Taipei, N/A, Taiwan - Republic of China
2 Inst. Mol. Biol., Academia Sinica, Taipei, N/A, Taiwan - Republic of China; , Taiwan - Republic of China
* To whom correspondence should be addressed. E-mail: yinghue{at}gate.sinica.edu.tw.
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 down-regulated. 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.
