Expression of hepatocyte nuclear factor 6 in rat liver is sex-dependent and regulated by growth hormone

被引:89
作者
Lahuna, O
Fernandez, L
Karlsson, H
Maiter, D
Lemaigre, FP
Rousseau, GG
Gustafsson, JA
Mode, A
机构
[1] KAROLINSKA INST,DEPT MED NUTR,S-14186 HUDDINGE,SWEDEN
[2] UNIV CATHOLIQUE LOUVAIN,SCH MED,UNITE DIABETOL,B-1200 BRUSSELS,BELGIUM
关键词
CYP2C12; gene transcription; hepatocyte nuclear factor 3; homeoproteins; sexual dimorphism;
D O I
10.1073/pnas.94.23.12309
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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,vith 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.
引用
收藏
页码:12309 / 12313
页数:5
相关论文
共 37 条
[1]   Molecular mechanism of growth hormone action [J].
CarterSu, C ;
Schwartz, J ;
Smit, LS .
ANNUAL REVIEW OF PHYSIOLOGY, 1996, 58 :187-207
[2]   ISOLATION OF BIOLOGICALLY-ACTIVE RIBONUCLEIC-ACID FROM SOURCES ENRICHED IN RIBONUCLEASE [J].
CHIRGWIN, JM ;
PRZYBYLA, AE ;
MACDONALD, RJ ;
RUTTER, WJ .
BIOCHEMISTRY, 1979, 18 (24) :5294-5299
[3]   EARLY RESPONSES OF TRANSACTIVATING FACTORS TO GROWTH-HORMONE IN PREADIPOCYTES - DIFFERENTIAL REGULATION OF CCAAT ENHANCER-BINDING PROTEIN-BETA (C/EBP-BETA) AND C/EBP-DELTA [J].
CLARKSON, RWE ;
CHEN, CM ;
HARRISON, S ;
WELLS, C ;
MUSCAT, GEO ;
WATERS, MJ .
MOLECULAR ENDOCRINOLOGY, 1995, 9 (01) :108-120
[4]   MULTIPLE HEPATOCYTE-ENRICHED NUCLEAR FACTORS FUNCTION IN THE REGULATION OF TRANSTHYRETIN AND ALPHA-1-ANTITRYPSIN GENES [J].
COSTA, RH ;
GRAYSON, DR ;
DARNELL, JE .
MOLECULAR AND CELLULAR BIOLOGY, 1989, 9 (04) :1415-1425
[5]   EFFECT OF GROWTH-HORMONE ON CARBOHYDRATE AND LIPID-METABOLISM [J].
DAVIDSON, MB .
ENDOCRINE REVIEWS, 1987, 8 (02) :115-131
[6]   GROWTH-HORMONE STIMULATES C-FOS GENE-EXPRESSION BY MEANS OF PROTEIN KINASE-C WITHOUT INCREASING INOSITOL LIPID TURNOVER [J].
DOGLIO, A ;
DANI, C ;
GRIMALDI, P ;
AILHAUD, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (04) :1148-1152
[7]   AGE-RELATED AND SEX-RELATED DIFFERENCES IN EPISODIC GROWTH-HORMONE SECRETION IN THE RAT [J].
EDEN, S .
ENDOCRINOLOGY, 1979, 105 (02) :555-560
[8]   SITE-DIRECTED MUTAGENESIS BY OVERLAP EXTENSION USING THE POLYMERASE CHAIN-REACTION [J].
HO, SN ;
HUNT, HD ;
HORTON, RM ;
PULLEN, JK ;
PEASE, LR .
GENE, 1989, 77 (01) :51-59
[9]   THE HEPATOCYTE NUCLEAR FACTOR-III FORKHEAD TRANSCRIPTION REGULATORY FAMILY IN DEVELOPMENT, INFLAMMATION, AND NEOPLASIA [J].
HROMAS, R ;
COSTA, R .
CRITICAL REVIEWS IN ONCOLOGY/HEMATOLOGY, 1995, 20 (1-2) :129-140
[10]  
ISAKSSON OGP, 1985, ANNU REV PHYSIOL, V47, P483, DOI 10.1146/annurev.ph.47.030185.002411