help button home button Endocrine Society Molecular Endocrinology ENDO 08 Sessions Library
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints, Permissions and Rights
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lahuna, O.
Right arrow Articles by Rousseau, G. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lahuna, O.
Right arrow Articles by Rousseau, G. G.
Molecular Endocrinology 14 (2): 285-294
Copyright © 2000 by The Endocrine Society

Involvement of STAT5 (Signal Transducer and Activator of Transcription 5) and HNF-4 (Hepatocyte Nuclear Factor 4) in the Transcriptional Control of the hnf6 Gene by Growth Hormone

Olivier Lahuna1,2, Mojgan Rastegar2, Dominique Maiter, Jean-Paul Thissen, Frédéric P. Lemaigre and Guy G. Rousseau

Hormone and Metabolic Research Unit (O.L., M.R., F.P.L., G.G.R.) Christian de Duve Institute of Cellular Pathology Unité de Diabétologie (D.M., J.-P.T.) Université catholique de Louvain B-1200 Brussels, Belgium

HNF-6 is a tissue-restricted transcription factor that participates in the regulation of several genes in liver. We reported earlier that in adult rats, HNF-6 mRNA concentration in liver drops to almost undetectable levels after hypophysectomy and returns to normal after 1 week of GH treatment. We now show that this results from a rapid effect of GH, and we characterize its molecular mechanism. In hypophysectomized rats, HNF-6 mRNAs increased within 1 h after a single injection of GH. The same GH-dependent induction was reproduced on isolated hepatocytes. To determine whether GH regulates hnf6 expression at the gene level, we studied its promoter. DNA binding experiments showed that 1) the transcription factors STAT5 (signal transducer and activator of transcription 5) and HNF-4 (hepatocyte nuclear factor 4) bind to sites located around -110 and -650, respectively; and 2) STAT5 binding is induced and HNF-4 binding affinity is increased in liver within 1 h after GH injection to hypophysectomized rats. Using transfection experiments and site-directed mutagenesis, we found that STAT5 and HNF-4 stimulated transcription of an hnf6 gene promoter-reporter construct. Furthermore, GH stimulated transcription of this construct in cells that express GH receptors. Consistent with our earlier finding that HNF-6 stimulates the hnf4 and hnf3ß gene promoters, GH treatment of hypophysectomized rats increased the liver concentration of HNF-4 and HNF-3ß mRNAs. Together, these data demonstrate that GH stimulates transcription of the hnf6 gene by a mechanism involving STAT5 and HNF-4. They show that HNF-6 participates not only as an effector, but also as a target, to the regulatory network of liver transcription factors, and that several members of this network are GH regulated.




This article has been cited by other articles:


Home page
 Mol. Endocrinol.Home page
S. Eleswarapu, X. Ge, Y. Wang, J. Yu, and H. Jiang
Growth Hormone-Activated STAT5 May Indirectly Stimulate IGF-I Gene Transcription through HNF-3{gamma}
Mol. Endocrinol., December 1, 2009; 23(12): 2026 - 2037.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
R. D. Meyer, E. V. Laz, T. Su, and D. J. Waxman
Male-Specific Hepatic Bcl6: Growth Hormone-Induced Block of Transcription Elongation in Females and Binding to Target Genes Inversely Coordinated with STAT5
Mol. Endocrinol., November 1, 2009; 23(11): 1914 - 1926.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
E. V. Laz, A. Sugathan, and D. J. Waxman
Dynamic in Vivo Binding of STAT5 to Growth Hormone-Regulated Genes in Intact Rat Liver. Sex-Specific Binding at Low- But Not High-Affinity STAT5 Sites
Mol. Endocrinol., August 1, 2009; 23(8): 1242 - 1254.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
E. F. Gevers, M. J. Hannah, M. J. Waters, and I. C. A. F. Robinson
Regulation of Rapid Signal Transducer and Activator of Transcription-5 Phosphorylation in the Resting Cells of the Growth Plate and in the Liver by Growth Hormone and Feeding
Endocrinology, August 1, 2009; 150(8): 3627 - 3636.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
D. J. Waxman and M. G. Holloway
Sex Differences in the Expression of Hepatic Drug Metabolizing Enzymes
Mol. Pharmacol., August 1, 2009; 76(2): 215 - 228.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Lu, G. B. Rha, M. Melikishvili, G. Wu, B. C. Adkins, M. G. Fried, and Y.-I. Chi
Structural Basis of Natural Promoter Recognition by a Unique Nuclear Receptor, HNF4{alpha}: DIABETES GENE PRODUCT
J. Biol. Chem., November 28, 2008; 283(48): 33685 - 33697.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
V. Wauthier and D. J. Waxman
Sex-Specific Early Growth Hormone Response Genes in Rat Liver
Mol. Endocrinol., August 1, 2008; 22(8): 1962 - 1974.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. Wang, M. Chen, G. Zheng, B. Dillard, M. Tallarico, Z. Ortiz, and A.-X. Holterman
Transcriptional activation by growth hormone of HNF-6-regulated hepatic genes, a potential mechanism for improved liver repair during biliary injury in mice
Am J Physiol Gastrointest Liver Physiol, August 1, 2008; 295(2): G357 - G366.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
T. Hashita, T. Sakuma, M. Akada, A. Nakajima, H. Yamahara, S. Ito, H. Takesako, and N. Nemoto
Forkhead Box A2-Mediated Regulation of Female-Predominant Expression of the Mouse Cyp2b9 Gene
Drug Metab. Dispos., June 1, 2008; 36(6): 1080 - 1087.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
M. G. Holloway, G. D. Miles, A. A. Dombkowski, and D. J. Waxman
Liver-Specific Hepatocyte Nuclear Factor-4{alpha} Deficiency: Greater Impact on Gene Expression in Male than in Female Mouse Liver
Mol. Endocrinol., May 1, 2008; 22(5): 1274 - 1286.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. J. DiGirolamo, A. Mukherjee, K. Fulzele, Y. Gan, X. Cao, S. J. Frank, and T. L. Clemens
Mode of Growth Hormone Action in Osteoblasts
J. Biol. Chem., October 26, 2007; 282(43): 31666 - 31674.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
E. V. Laz, M. G. Holloway, C.-S. Chen, and D. J. Waxman
Characterization of Three Growth Hormone-Responsive Transcription Factors Preferentially Expressed in Adult Female Liver
Endocrinology, July 1, 2007; 148(7): 3327 - 3337.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
H. Jiang, Y. Wang, M. Wu, Z. Gu, S. J. Frank, and R. Torres-Diaz
Growth Hormone Stimulates Hepatic Expression of Bovine Growth Hormone Receptor Messenger Ribonucleic Acid through Signal Transducer and Activator of Transcription 5 Activation of a Major Growth Hormone Receptor Gene Promoter
Endocrinology, July 1, 2007; 148(7): 3307 - 3315.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
O. M. Vidal, R. Merino, E. Rico-Bautista, L. Fernandez-Perez, D. J. Chia, J. Woelfle, M. Ono, B. Lenhard, G. Norstedt, P. Rotwein, et al.
In Vivo Transcript Profiling and Phylogenetic Analysis Identifies Suppressor of Cytokine Signaling 2 as a Direct Signal Transducer and Activator of Transcription 5b Target in Liver
Mol. Endocrinol., January 1, 2007; 21(1): 293 - 311.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
D. J. Waxman and C. O'Connor
Growth Hormone Regulation of Sex-Dependent Liver Gene Expression
Mol. Endocrinol., November 1, 2006; 20(11): 2613 - 2629.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
M. G. Holloway, E. V. Laz, and D. J. Waxman
Codependence of Growth Hormone-Responsive, Sexually Dimorphic Hepatic Gene Expression on Signal Transducer and Activator of Transcription 5b and Hepatic Nuclear Factor 4{alpha}
Mol. Endocrinol., March 1, 2006; 20(3): 647 - 660.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. J. Chia, M. Ono, J. Woelfle, M. Schlesinger-Massart, H. Jiang, and P. Rotwein
Characterization of Distinct Stat5b Binding Sites That Mediate Growth Hormone-stimulated IGF-I Gene Transcription
J. Biol. Chem., February 10, 2006; 281(6): 3190 - 3197.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
A. V. Poll, C. E. Pierreux, L. Lokmane, C. Haumaitre, Y. Achouri, P. Jacquemin, G. G. Rousseau, S. Cereghini, and F. P. Lemaigre
A vHNF1/TCF2-HNF6 Cascade Regulates the Transcription Factor Network That Controls Generation of Pancreatic Precursor Cells
Diabetes, January 1, 2006; 55(1): 61 - 69.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
J. Xu, S. Ji, D. Y Venable, J. L Franklin, and J. L Messina
Prolonged insulin treatment inhibits GH signaling via STAT3 and STAT1
J. Endocrinol., March 1, 2005; 184(3): 481 - 492.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. A. Wiwi and D. J. Waxman
Role of Hepatocyte Nuclear Factors in Transcriptional Regulation of Male-specific CYP2A2
J. Biol. Chem., February 4, 2005; 280(5): 3259 - 3268.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. E. Rowland, A. M. Lichanska, L. M. Kerr, M. White, E. M. d'Aniello, S. L. Maher, R. Brown, R. D. Teasdale, P. G. Noakes, and M. J. Waters
In Vivo Analysis of Growth Hormone Receptor Signaling Domains and Their Associated Transcripts
Mol. Cell. Biol., January 1, 2005; 25(1): 66 - 77.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
S Eleswarapu and H Jiang
Growth hormone regulates the expression of hepatocyte nuclear factor-3 gamma and other liver-enriched transcription factors in the bovine liver
J. Endocrinol., January 1, 2005; 184(1): 95 - 105.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
K.-C. Leung, G. Johannsson, G. M. Leong, and K. K. Y. Ho
Estrogen Regulation of Growth Hormone Action
Endocr. Rev., October 1, 2004; 25(5): 693 - 721.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
C. A. Wiwi, M. Gupte, and D. J. Waxman
Sexually Dimorphic P450 Gene Expression in Liver-Specific Hepatocyte Nuclear Factor 4{alpha}-Deficient Mice
Mol. Endocrinol., August 1, 2004; 18(8): 1975 - 1987.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
D. J. Waxman and J. L. Celenza
Sexual dimorphism of hepatic gene expression: novel biological role of KRAB zinc finger repressors revealed
Genes & Dev., November 1, 2003; 17(21): 2607 - 2613.
[Full Text] [PDF]

Home page
 DevelopmentHome page
F. Clotman, V. J. Lannoy, M. Reber, S. Cereghini, D. Cassiman, P. Jacquemin, T. Roskams, G. G. Rousseau, and F. P. Lemaigre
The onecut transcription factor HNF6 is required for normal development of the biliary tract
Development, March 6, 2003; 129(8): 1819 - 1828.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
Y. E. Timsit and D. S. Riddick
Stimulation of Hepatic Signal Transducer and Activator of Transcription 5b by GH Is Not Altered by 3-Methylcholanthrene
Endocrinology, September 1, 2002; 143(9): 3284 - 3294.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
H. Helander, J.-A. Gustafsson, and A. Mode
Possible Involvement of Truncated Signal Transducer and Activator of Transcription-5 in the GH Pattern-Dependent Regulation of CYP2C12 Gene Expression in Rat Liver
Mol. Endocrinol., July 1, 2002; 16(7): 1598 - 1611.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
J. E. Dumont, S. Dremier, I. Pirson, and C. Maenhaut
Cross signaling, cell specificity, and physiology
Am J Physiol Cell Physiol, July 1, 2002; 283(1): C2 - C28.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
H. Schrem, J. Klempnauer, and J. Borlak
Liver-Enriched Transcription Factors in Liver Function and Development. Part I: The Hepatocyte Nuclear Factor Network and Liver-Specific Gene Expression
Pharmacol. Rev., March 1, 2002; 54(1): 129 - 158.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S.-H. Park and D. J. Waxman
Inhibitory Cross-talk between STAT5b and Liver Nuclear Factor HNF3beta . IMPACT ON THE REGULATION OF GROWTH HORMONE PULSE-STIMULATED, MALE-SPECIFIC LIVER CYTOCHROME P-450 GENE EXPRESSION
J. Biol. Chem., November 9, 2001; 276(46): 43031 - 43039.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
A. Bailly, M. E. Torres-Padilla, A. P. Tinel, and M. C. Weiss
An enhancer element 6 kb upstream of the mouse HNF4{alpha}1 promoter is activated by glucocorticoids and liver-enriched transcription factors
Nucleic Acids Res., September 1, 2001; 29(17): 3495 - 3505.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. Eeckhoute, P. Formstecher, and B. Laine
Maturity-Onset Diabetes of the Young Type 1 (MODY1)-Associated Mutations R154X and E276Q in Hepatocyte Nuclear Factor 4{{alpha}} (HNF4{{alpha}}) Gene Impair Recruitment of p300, a Key Transcriptional Coactivator
Mol. Endocrinol., July 1, 2001; 15(7): 1200 - 1210.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
H. K. Choi and D. J. Waxman
Plasma Growth Hormone Pulse Activation of Hepatic JAK-STAT5 Signaling: Developmental Regulation and Role in Male-Specific Liver Gene Expression
Endocrinology, September 1, 2000; 141(9): 3245 - 3255.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. Rastegar, G. G. Rousseau, and F. P. Lemaigre
CCAAT/Enhancer-Binding Protein-{alpha} Is a Component of the Growth Hormone-Regulated Network of Liver Transcription Factors
Endocrinology, May 1, 2000; 141(5): 1686 - 1692.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. J. Lannoy, A. Rodolosse, C. E. Pierreux, G. G. Rousseau, and F. P. Lemaigre
Transcriptional Stimulation by Hepatocyte Nuclear Factor-6. TARGET-SPECIFIC RECRUITMENT OF EITHER CREB-BINDING PROTEIN (CBP) or p300/CBP-ASSOCIATED FACTOR (p/CAF)
J. Biol. Chem., July 14, 2000; 275(29): 22098 - 22103.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. B. Ehret, P. Reichenbach, U. Schindler, C. M. Horvath, S. Fritz, M. Nabholz, and P. Bucher
DNA Binding Specificity of Different STAT Proteins. COMPARISON OF IN VITRO SPECIFICITY WITH NATURAL TARGET SITES
J. Biol. Chem., February 23, 2001; 276(9): 6675 - 6688.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Delesque-Touchard, S.-H. Park, and D. J. Waxman
Synergistic Action of Hepatocyte Nuclear Factors 3 and 6 on CYP2C12 Gene Expression and Suppression by Growth Hormone-activated STAT5b. PROPOSED MODEL FOR FEMALE-SPECIFIC EXPRESSION OF CYP2C12 IN ADULT RAT LIVER
J. Biol. Chem., October 27, 2000; 275(44): 34173 - 34182.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. S. Streeper, L. A. Hornbuckle, C. A. Svitek, J. K. Goldman, J. K. Oeser, and R. M. O'Brien
Protein Kinase A Phosphorylates Hepatocyte Nuclear Factor-6 and Stimulates Glucose-6-phosphatase Catalytic Subunit Gene Transcription
J. Biol. Chem., May 25, 2001; 276(22): 19111 - 19118.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2000 by The Endocrine Society