Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/75974
Title: Expression of hepatocyte nuclear factor 6 in rat liver is sex-dependent and regulated by growth hormone
Authors: Lahuna, Olivier
Fernández Pérez, Leandro Fco 
Karlsson, Hanna
Maiter, Dominique
Lemaigre, Frederic P.
Rousseau, Guy G.
Gustafsson, Jan Åke
Mode, Agneta
UNESCO Clasification: 2302 Bioquímica
2407 Biología celular
3201 Ciencias clínicas
3209 Farmacología
Keywords: Cyp2C12
Gene Transcription
Hepatocyte Nuclear Factor 3
Homeoproteins
Sexual Dimorphism
Issue Date: 1997
Journal: Proceedings of the National Academy of Sciences of the United States of America 
Abstract: Growth hormone (GH) binding to its receptor modulates gene transcription by influencing the amount or activity of transcription factors. In the rat, GH exerts sexually dimorphic effects on liver gene transcription through its pattern of secretion which is intermittent in males and continuous in females. The expression of the CYP2C12 gene coding for the female-specific cytochrome P450 2C12 protein is dependent on the continuous exposure to GH. To identify the transcription factor(s) that mediate(s) this sex-dependent GH effect, we studied the interactions of the CYP2C12 promoter with liver nuclear proteins obtained from male and female rats and from hypophysectomized animals treated or not by continuous GH infusion. GH treatment induced the binding of a protein that we identified as hepatocyte nuclear factor (HNF) 6, the prototype of a novel class of homeodomain transcription factors. HNF-6 competed with HNF-3 for binding to the same site in the CYP2C12 promoter. This HNF-6/HNF-3 binding site conveyed both HNF-6- and HNF-3-stimulated transcription of a reporter gene construct in transient cotransfection experiments. Electrophoretic mobility shift assays showed more HNF-6 DNA-binding activity in female than in male liver nuclear extracts. Liver HNF-6 mRNA was barely detectable in the hypophysectomized rats and was restored to normal levels by GH treatment. This work provides an example of a homeodomain-containing transcription factor that is GH-regulated and also reports on the hormonal regulation of HNF-6.
URI: http://hdl.handle.net/10553/75974
ISSN: 0027-8424
DOI: 10.1073/pnas.94.23.12309
Source: Proceedings of the National Academy of Sciences of the United States of America [ISSN 0027-8424], v. 94 (23), p. 12309-12313, (Noviembre 1997)
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