scholarly journals Multiple Distant STAT5 Binding Sites Mediate Growth Hormone Regulation of IGF‐I Gene Expression

2007 ◽  
Vol 21 (6) ◽  
Author(s):  
Honglin Jiang ◽  
Satyanaryana Eleswarapu ◽  
Zhiliang Gu ◽  
Ying Wang ◽  
Bettina Heid
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Binding Sites ◽  
Hormone Regulation ◽  
Igf I ◽  
I Gene

scholarly journals Growth Hormone Regulation of Insulin-Like Growth Factor-I Gene Expression May Be Mediated by Multiple Distal Signal Transducer and Activator of Transcription 5 Binding Sites

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2230-2240 ◽  
Author(s):  
Satyanaryana Eleswarapu ◽  
Zhiliang Gu ◽  
Honglin Jiang
Keyword(s):  
Gene Expression ◽  
Reporter Gene ◽  
Binding Sites ◽  
Mouse Liver ◽  
Consensus Sequence ◽  
Reporter Gene Expression ◽  
Hormone Regulation ◽  
Signal Transducer ◽  
Igf I ◽  
I Gene

The transcription factor signal transducer and activator of transcription (STAT)-5 mediates GH stimulation of IGF-I gene expression in the liver. Previous studies suggested that STAT5 might exert this effect by binding to an IGF-I intron 2 region and a distal 5′-flanking region each containing two STAT5 binding sites. Here we report the identification of three additional chromosomal regions containing a total of five putative STAT5 binding sites that may mediate GH-induced STAT5 activation of IGF-I gene expression in the mouse liver. By comparing an 170-kb mouse genomic DNA containing the IGF-I gene with the corresponding human sequence, we identified 19 putative STAT5 binding sites that bear the consensus sequence of STAT5 binding site and are conserved across the two species. Chromatin immunoprecipitation assays indicated that five chromosomal regions containing a total of nine of the 19 putative STAT5 binding sites were bound by STAT5 in the mouse liver in response to GH administration and that these bindings preceded or coincided with GH-increased IGF-I gene transcription. Two of the five chromosomal regions correspond to those previously identified in other species, and the three new chromosomal regions that contain a total of five putative STAT5 binding sites are IGF-I intron 3 regions located at least 26 kb from the transcription start site. Gel-shift assays confirmed the binding of the five new putative STAT5 binding sites as well as three of the four previously identified STAT5 binding sites to GH-activated STAT5 from the mouse liver. Cotransfection analyses indicated that, although each of the five chromosomal regions was able to mediate STAT5 activation of reporter gene expression, together they mediated greater STAT5 activation of reporter gene expression in response to GH. Overall, these results suggest that GH-induced STAT5 activation of IGF-I gene expression in the mouse liver might be collectively mediated by at least eight STAT5 binding sites located in distal intronic and 5′-flanking regions of the IGF-I gene.

scholarly journals Identifying growth hormone-regulated enhancers in the Igf1 locus

2015 ◽  
Vol 47 (11) ◽  
pp. 559-568 ◽  
Author(s):  
Damir Alzhanov ◽  
Aditi Mukherjee ◽  
Peter Rotwein
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Gene Transcription ◽  
Somatic Growth ◽  
Gene Promoters ◽  
Chromosomal Locus ◽  
Transcriptional Enhancers ◽  
Physiological Processes ◽  
Igf I ◽  
I Gene

Growth hormone (GH) plays a central role in regulating somatic growth and in controlling multiple physiological processes in humans and other vertebrates. A key agent in many GH actions is the secreted peptide, IGF-I. As established previously, GH stimulates IGF-I gene expression via the Stat5b transcription factor, leading to production of IGF-I mRNAs and proteins. However, the precise mechanisms by which GH-activated Stat5b promotes IGF-I gene transcription have not been defined. Unlike other GH-regulated genes, there are no Stat5b sites near either of the two IGF-I gene promoters. Although dispersed GH-activated Stat5b binding elements have been mapped in rodent Igf1 gene chromatin, it is unknown how these distal sites might function as potential transcriptional enhancers. Here we have addressed mechanisms of regulation of IGF-I gene transcription by GH by generating cell lines in which the rat Igf1 chromosomal locus has been incorporated into the mouse genome. Using these cells we find that physiological levels of GH rapidly and potently activate Igf1 gene transcription while stimulating physical interactions in chromatin between inducible Stat5b-binding elements and the Igf1 promoters. We have thus developed a robust experimental platform for elucidating how dispersed transcriptional enhancers control Igf1 gene expression under different biological conditions.

scholarly journals 20kDa Human Growth Hormone (20K hGH) Stimulates Insulin-Like Growth Factor-I (IGF-I) Gene Expression at Lower Concentrations than 22K hGH in hGH Receptor-Expressing Ba/F3 Cells

2000 ◽  
Vol 47 (SupplMarch) ◽  
pp. S37-S40 ◽  
Author(s):  
HIDEO YOSHIZATO ◽  
MINORU TANAKA ◽  
TAKAHIKO FUJIKAWA ◽  
YOSHIFUMI HIGASHIMOTO ◽  
AYAKO SHIMIZU ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Growth Factor ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
I Gene

GH insensitivity induced by endotoxin injection is associated with decreased liver GH receptors

1999 ◽  
Vol 276 (3) ◽  
pp. E565-E572 ◽  
Author(s):  
Dominique Defalque ◽  
Nathalie Brandt ◽  
Jean-Marie Ketelslegers ◽  
Jean-Paul Thissen
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Growth Factor ◽  
Binding Sites ◽  
Anabolic Hormone ◽  
Gh Receptor ◽  
Its Gene ◽  
Igf I ◽  
Gh Receptors ◽  
Gh Resistance

Sepsis induces a state of growth hormone (GH) resistance associated with a decrease of circulating insulin-like growth factor (IGF) I, a GH-dependent anabolic hormone mainly produced by the liver. To address the mechanisms that might trigger GH insensitivity in sepsis, we investigated the regulation of liver GH receptor (GHR) and its gene expression by endotoxin. Endotoxin injection in rats decreased serum IGF-I and liver GH-binding sites after 10 h. In contrast to liver GHR, circulating GH-binding protein (GHBP) levels were not significantly reduced after endotoxin injection. The parallel decrease in IGF-I and GHR and in their corresponding liver mRNAs suggests that decreased serum IGF-I and liver GHR were likely to result from decreased liver synthesis. Although GH administration in control animals significantly enhanced serum IGF-I, it did fail to prevent the decline in serum IGF-I and liver GH-binding sites in endotoxemic rats. In this study, we showed that endotoxin injection induces a state of GH insensitivity associated with decreased liver GHR. This decline in GHR, which cannot be prevented by exogenous GH, might contribute to the GH insensitivity observed in sepsis.

scholarly journals Control of ovine hepatic growth hormone receptor and insulin-like growth factor I by thyroid hormones in utero

2000 ◽  
Vol 278 (6) ◽  
pp. E1166-E1174 ◽  
Author(s):  
A. J. Forhead ◽  
J. Li ◽  
J. C. Saunders ◽  
M. J. Dauncey ◽  
R. S. Gilmour ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Growth Factor ◽  
Thyroid Hormones ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
I Gene

By use of RNase protection assays, hepatic growth hormone receptor (GHR) and insulin-like growth factor I (IGF-I) mRNA abundances were measured in sheep fetuses after experimental manipulation of fetal plasma thyroid hormone concentrations by fetal thyroidectomy (TX) and exogenous infusion of triiodothyronine (T3) and cortisol. TX abolished the normal prepartum rise in hepatic GHR abundance but had little effect on hepatic GHR gene expression at 127–130 days (term 145 ± 2 days). By contrast, it upregulated basal IGF-I expression in immature fetal liver by increasing both Class 1 and Class 2 transcript abundance but had no further effects on IGF-I gene mRNA levels at 142–145 days. Raising plasma T3 to prepartum values by exogenous infusion of either T3 or cortisol into immature intact fetuses prematurely raised hepatic GHR and IGF-I mRNA abundances to values similar to those seen in intact fetuses at 142–145 days. In TX fetuses, cortisol infusion increased hepatic GHR mRNA but not total IGF-I mRNA abundance at 127–130 days. These findings show that thyroid hormones have an important role in the regulation of hepatic GHR and IGF-I gene expression in fetal sheep during late gestation and suggest that T3 mediates the maturational effects of cortisol on the hepatic somatotropic axis close to term.

Growth hormone stimulates IGF I gene expression in isolated rat renal collecting duct

1990 ◽  
Vol 259 (3) ◽  
pp. F474-F479 ◽  
Author(s):  
S. A. Rogers ◽  
S. B. Miller ◽  
M. R. Hammerman
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Plasma Membranes ◽  
Collecting Duct ◽  
Dependent Manner ◽  
Collecting Ducts ◽  
Igf I ◽  
Renal Collecting Duct ◽  
I Gene

To determine whether growth hormone (GH) directly stimulates insulin-like growth factor I (IGF I) gene expression in renal collecting duct, plasma membranes prepared from collecting ducts isolated from rat kidney, and collecting ducts themselves were incubated in presence and absence of GH. GH enhanced phospholipase C activity in collecting duct plasma membranes establishing the potential for GH-signal transduction. Inclusion of GH in suspensions of collecting ducts increased production of immunoreactive IGF I in a time-dependent and concentration-dependent manner. Production was stimulated significantly by addition of 10(-10), 10(-8), or 10(-6) M GH to suspensions for 2 h. IGF I produced in isolated collecting ducts was released into the suspending media. Levels of IGF I mRNA in collecting ducts were increased 2.8-fold after incubation with 10(-6) M GH in vitro. IGF I of collecting duct origin was indistinguishable from recombinant human IGF I in terms of its size and receptor-binding characteristics. Our findings demonstrate a direct action of GH to enhance collecting duct IGF I gene expression in vitro. Such enhancement is likely to reflect the mechanism by which GH stimulates renal IGF I production in intact kidney.

Continuous administration of growth hormone does not prevent the decrease of IGF-I gene expression in zinc-deprived rats despite normalization of liver GH binding

1998 ◽  
Vol 8 (6) ◽  
pp. 465-472 ◽  
Author(s):  
N.X. Ninh ◽  
D. Maiter ◽  
P. Lause ◽  
B. Chrzanowska ◽  
L.E. Underwood ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Continuous Administration ◽  
Igf I ◽  
I Gene
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