Regulation of growth hormone receptor gene expression

被引:73
作者
Schwartzbauer, G
Menon, RK
机构
[1] Division of Endocrinology, Department of Pediatrics, Univ. of Pittsburgh Sch. of Medicine, Pittsburgh
关键词
D O I
10.1006/mgme.1998.2685
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Pituitary growth hormone (C:H) is essential for postnatal growth in animals. GH exerts its actions by direct effect on target organs and by stimulating the production of insulin-like growth factor I (IGF-I). At the tissue level, the pleiotropic actions of G;H result from the interaction of GH with a specific cell surface receptor, the GH receptor (GHR). The GHR belongs to the hematopoietic receptor superfamily. The human GHR is the product of a single gene located on chromosome 5p13.1-p12 and spans at least 87 kb. Transcripts from this gene are characterized by the presence of disparate 5' untranslated exons. In the liver at least eight different GHR 5' untranslated regions (UTRs) have been described. This heterogeneity in the 5' UTR most likely results from the splicing of the various exon 1 fragments to a common splice site located 11 bp upstream of the initiating ATG. Heterogeneity in the 5' UTR sequences of the GHR transcripts indicates that transcriptional control of the locus is complex. GHR gene expression is minimal to absent in the fetus, with the postnatal increase in expression in the liver being maximal during pregnancy. GHR gene expression is also regulated by factors such as nutritional intake, GH, steroid hormones, and diabetes mellitus. Available information about the molecular mechanisms regulating expression of the GHR gene is discussed. Thus the GHR gene presents a picture of multiple 5' untranslated exons under the control of multiple promoters. The use of alternate promoters for initiation of transcription in conjunction with differential splicing allows for exquisite regulation of gene expression. This schema is appropriate for a protein that is essential to many of the physiological processes that are crucial for the survival and well-being of the organism. (C) 1998 Academic Press.
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页码:243 / 253
页数:11
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共 101 条
[11]   Differential regulation of the growth hormone receptor gene: Effects of dexamethasone and estradiol [J].
Bennett, PA ;
Levy, A ;
Carmignac, DF ;
Robinson, ICAF ;
Lightman, SL .
ENDOCRINOLOGY, 1996, 137 (09) :3891-3896
[12]   REGULATION OF INSULIN-LIKE GROWTH FACTOR-I AND GROWTH-HORMONE RECEPTOR GENE-EXPRESSION BY DIABETES AND NUTRITIONAL STATE IN RAT-TISSUES [J].
BORNFELDT, KE ;
ARNQVIST, HJ ;
ENBERG, B ;
MATHEWS, LS ;
NORSTEDT, G .
JOURNAL OF ENDOCRINOLOGY, 1989, 122 (03) :651-656
[13]   THE INDUCTION OF HEPATIC SOMATOTROPIC RECEPTORS AFTER BIRTH IN SHEEP IS DEPENDENT ON PARTURITION-ASSOCIATED MECHANISMS [J].
BREIER, BH ;
AMBLER, GR ;
SAUERWEIN, H ;
SURUS, A ;
GLUCKMAN, PD .
JOURNAL OF ENDOCRINOLOGY, 1994, 141 (01) :101-108
[14]   THE SOMATOTROPIC AXIS IN YOUNG STEERS - INFLUENCE OF NUTRITIONAL-STATUS AND OESTRADIOL-17-BETA ON HEPATIC HIGH-AFFINITY AND LOW-AFFINITY SOMATOTROPIC BINDING-SITES [J].
BREIER, BH ;
GLUCKMAN, PD ;
BASS, JJ .
JOURNAL OF ENDOCRINOLOGY, 1988, 116 (02) :169-177
[15]   INFLUENCE OF NUTRITIONAL-STATUS AND OESTRADIOL-17-BETA ON PLASMA GROWTH-HORMONE, INSULIN-LIKE GROWTH FACTOR-I AND FACTOR-II AND THE RESPONSE TO EXOGENOUS GROWTH-HORMONE IN YOUNG STEERS [J].
BREIER, BH ;
GLUCKMAN, PD ;
BASS, JJ .
JOURNAL OF ENDOCRINOLOGY, 1988, 118 (02) :243-250
[16]   PLASMA-CONCENTRATIONS OF INSULIN-LIKE GROWTH FACTOR-I AND INSULIN IN THE INFANT CALF - ONTOGENY AND INFLUENCE OF ALTERED NUTRITION [J].
BREIER, BH ;
GLUCKMAN, PD ;
BASS, JJ .
JOURNAL OF ENDOCRINOLOGY, 1988, 119 (01) :43-50
[17]   ADRENAL INVOLVEMENT IN THE DIABETES-INDUCED LOSS OF GROWTH-HORMONE AND PROLACTIN RECEPTORS IN THE LIVERS OF FEMALE RATS [J].
BRYSON, JM ;
BAXTER, RC .
DIABETOLOGIA, 1986, 29 (02) :106-111
[18]   Liver and kidney growth hormone (GH) receptors are regulated differently in diabetic GH and GH antagonist transgenic mice [J].
Chen, NY ;
Chen, WY ;
Kopchick, JJ .
ENDOCRINOLOGY, 1997, 138 (05) :1988-1994
[19]   CHARACTERIZATION OF PORCINE GROWTH-HORMONE (PGH) BINDING TO PORCINE LIVER-MICROSOMES - CHRONIC ADMINISTRATION OF PGH INDUCES PGH BINDING [J].
CHUNG, CS ;
ETHERTON, TD .
ENDOCRINOLOGY, 1986, 119 (02) :780-786
[20]   PORCINE GROWTH-HORMONE RECEPTOR CDNA SEQUENCE [J].
CIOFFI, JA ;
WANG, X ;
KOPCHICK, JJ .
NUCLEIC ACIDS RESEARCH, 1990, 18 (21) :6451-6451