scholarly journals Growth Hormone Receptor Antagonism Prevents Early Renal in Nonobese Diabetic Mice

1999 ◽  
Vol 10 (11) ◽  
pp. 2374-2381
Author(s):  
YAEL SEGEV ◽  
DANIEL LANDAU ◽  
RUTH RASCH ◽  
ALLAN FLYVBJERG ◽  
MOSHE PHILLIP
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Receptor ◽  
Binding Protein ◽  
Somatic Growth ◽  
Nod Mice ◽  
Mrna Levels ◽  
Therapeutic Implications ◽  
Protein Levels ◽  
Nonobese Diabetic ◽  
Igf I

Abstract. The growth hormone (GH)/insulin-like growth factor (IGF) axis is involved in diabetic renal disease. The role of a specific GH receptor (GHR) antagonist in the development of early renal changes in nonobese diabetic (NOD) mice was investigated. Female diabetic (nonketotic) NOD mice treated with a polyethylene glycol-treated GHR antagonist (2 mg/kg, every other day) (DA group) or saline (D group) and their nonhyperglycemic age-matched littermates (control animals) were euthanized 3 wk after the onset of diabetes. Body weights at euthanasia were similar among the groups. Serum GH levels were markedly elevated, and serum IGF-I levels were significantly decreased in D and DA animals, compared with controls. The increases in kidney weights and glomerular volumes observed for the D group were absent in the DA group. Albuminuria was increased in the D group but was normalized in the DA group. Extractable renal IGF-I protein levels were increased in the D group but were partially normalized in the DA group. Renal IGF-binding protein 1 mRNA levels were increased in the D group but returned to almost normal levels in the DA animals. Kidney IGF-I and GHR mRNA levels were decreased in both the D and DA groups. Renal GH-binding protein mRNA levels remained unchanged in both diabetic groups. GHR antagonism had a blunting effect on renal/glomerular hypertrophy and albuminuria in diabetic NOD mice. These salutary effects were associated with concomitant inhibition of increased renal IGF-I protein levels and were obtained without affecting either somatic growth or circulating GH and IGF-I levels. Therefore, modulation of GH effects may have beneficial therapeutic implications in diabetic nephropathy.

The interrelationship between and the regulation of hepatic growth hormone receptors and circulating GH binding protein in the pig

1992 ◽  
Vol 126 (2) ◽  
pp. 155-161 ◽  
Author(s):  
Geoffrey R Ambler ◽  
Bernhard H Breier ◽  
Andrzej Surus ◽  
Hugh T Blair ◽  
Stuart N McCutcheon ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Receptor ◽  
Hormone Receptors ◽  
Binding Capacity ◽  
Binding Protein ◽  
Somatic Growth ◽  
Gh Receptor ◽  
Age Related ◽  
Igf I ◽  
Serum Gh

We evaluated the interrelationship between, and regulation of, the hepatic growth hormone receptor and serum GH binding protein (GH BP) in pigs treated with recombinant porcine growth hormone (rpGH). Infant and pubertal male pigs (N = 5 per group) received either rpGH 0.15 mg/kg daily or diluent intramuscularly for 12 days. Somatic growth, serum IGF-I and GH BP and [125I]bovine GH (bGH) binding to MgCl2-treated hepatic membrane homogenates were examined. Marked age-related increases were seen in serum GH BP (p<0.001) and [125I]bGH binding to hepatic membranes (p<0.001). GH BP was increased in rpGH treated animals (p = 0.03), from 13.8±1.2 (mean±1 x sem) (controls) to 17.8±2.0% in infants, and from 35.2±2.6 (controls) to 41.8±3.4% in pubertal animals. [125I]bGH binding to hepatic membranes was also increased by rpGH treatment (p<0.05), from 7.0±1.6 (controls) to 15.4±3.6% in infants and from 53.7±7.1 (controls) to 65.1±11.8% in pubertal animals. No significant interaction between age and treatment was seen. Overall, serum GH BP correlated significantly with [125I]bGH membrane capacity (r=0.82, p<0.001), with a correlation of r= 0.83 in the infant animals but no significant correlation in the pubertal animals considered alone (r=0.13). Serum IGF-I correlated significantly with serum GH BP (r=0.93, p<0.001) and [125]bGH membrane binding capacity (r = 0.91, p< 0.001). These observations suggest that serum GH BP levels reflect major changes of hepatic GH receptor status. In addition, the present study demonstrates that the hepatic GH receptor can be induced by GH in the infant pig, despite a developmentally low GH receptor population at this age, suggesting potential efficacy of GH at earlier ages than generally considered.

scholarly journals Dose-response effects of a new growth hormone receptor antagonist (B2036-PEG) on circulating, hepatic and renal expression of the growth hormone/insulin-like growth factor system in adult mice

2000 ◽  
Vol 167 (2) ◽  
pp. 295-303 ◽  
Author(s):  
JW van Neck ◽  
NF Dits ◽  
V Cingel ◽  
IA Hoppenbrouwers ◽  
SL Drop ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Receptor Antagonist ◽  
Growth Hormone Receptor ◽  
Binding Protein ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Gh Receptor ◽  
Igf I ◽  
Igfbp 3

The effects of growth hormone (GH) in regulating the expression of the hepatic and renal GH and insulin-like growth factor (IGF) system were studied by administering a novel GH receptor antagonist (GHRA) (B2036-PEG) at different doses (0, 1.25, 2.5, 5 and 10 mg/kg/day) to mice for 7 days. No differences were observed in the groups with respect to body weight, food consumption or blood glucose. However, a dose-dependent decrease was observed in circulating IGF-I levels and in hepatic and renal IGF-I levels at the highest doses. In contrast, in the 5 and 10 mg/kg/day GHRA groups, circulating and hepatic transcriptional IGF binding protein-3 (IGFBP-3) levels were not modified, likely resulting in a significantly decreased IGF-I/IGFBP-3 ratio. Hepatic GH receptor (GHR) and GH binding protein (GHBP) mRNA levels increased significantly in all GHRA dosage groups. Endogenous circulatory GH levels increased significantly in the 2.5 and 5 mg/kg/day GHRA groups. Remarkably, increased circulating IGFBP-4 and hepatic IGFBP-4 mRNA levels were observed in all GHRA administration groups. Renal GHR and GHBP mRNA levels were not modified by GHRA administration at the highest doses. Also, renal IGFBP-3 mRNA levels remained unchanged in most GHRA administration groups, whereas IGFBP-1, -4 and -5 mRNA levels were significantly increased in the 5 and 10 mg/kg/day GHRA administration groups. In conclusion, the effects of a specific GHR blockade on circulating, hepatic and renal GH/IGF axis reported here, may prove useful in the future clinical use of GHRAs.

Tumor necrosis factor inhibits growth hormone-mediated gene expression in hepatocytes

2006 ◽  
Vol 291 (1) ◽  
pp. G35-G44 ◽  
Author(s):  
Tamer Ahmed ◽  
Gladys Yumet ◽  
Margaret Shumate ◽  
Charles H. Lang ◽  
Peter Rotwein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Mrna Expression ◽  
Gene Transcription ◽  
Protein Tyrosine Phosphatases ◽  
Mrna Levels ◽  
Inhibitory Effects ◽  
Protein Levels ◽  
Mrna Induction ◽  
Igf I

Growth hormone (GH) stimulates STAT5 phosphorylation by JAK2, which activates IGF-I and serine protease inhibitor 2.1 (Spi 2.1) transcription, whereas STAT5 dephosphorylation by protein tyrosine phosphatases (PTPs) terminates this signal. We hypothesized that the inhibitory effects of TNF on GH signaling and gene transcription were responsible for hepatic GH resistance. CWSV-1 hepatocytes were treated with TNF, pervanadate (a PTP inhibitor), or both, before GH stimulation. Total and tyrosine-phosphorylated JAK2, STAT5, ERK1/2, SHP-1 and SHP-2, IGF-I, and Spi 2.1 mRNA levels were measured. GH stimulated STAT5 and ERK1/2 phosphorylation, IGF-I, and Spi 2.1 mRNA expression. TNF attenuated JAK2/STAT5 and ERK1/2 phosphorylation and IGF-I and Spi 2.1 mRNA expression following GH stimulation. SHP-1 and SHP-2 protein levels were unaltered by TNF or GH, and the GH-induced increase in SHP-1 PTP activity was not further increased by TNF. In TNF-treated cells, pervanadate restored STAT5 and ERK1/2 phosphorylation to control levels following GH stimulation but did not restore IGF-I or Spi 2.1 mRNA induction. Cells transfected with a Spi 2.1 promoter-luciferase vector demonstrate a 50-fold induction in luciferase activity following GH stimulation or cotransfection with a constitutively active STAT5 vector. TNF prevented the induction of Spi 2.1 promoter activity by GH and the STAT5 construct. We conclude that TNF does not inhibit GH activity by inducing SHP-1 or -2 expression and that correction of GH signaling defects in TNF-treated cells by pervanadate does not restore GH-induced gene expression. The inhibitory effects of TNF on GH-mediated gene transcription appear independent of STAT5 activity and previously identified abnormalities in JAK2/STAT5 signaling.

In rats with sepsis, the acute fall in IGF-I is associated with an increase in circulating growth hormone-binding protein levels

2000 ◽  
Vol 26 (10) ◽  
pp. 1547-1552 ◽  
Author(s):  
M.J. O'Leary ◽  
N. Quinton ◽  
C.N. Ferguson ◽  
V.R. Preedy ◽  
R.J.M. Ross ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Binding Protein ◽  
Hormone Binding ◽  
Protein Levels ◽  
Growth Hormone Binding Protein ◽  
Igf I ◽  
Hormone Binding Protein

scholarly journals Expression profiles of growth hormone receptor and insulin-like growth factor I in cattle and yak tissues revealed by quantitative real-time PCR

2013 ◽  
Vol 56 (1) ◽  
pp. 700-708
Author(s):  
J. . Pei ◽  
X. Lang ◽  
P. Bao ◽  
C. Liang ◽  
M. Chu ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Mammary Gland ◽  
Growth Factor ◽  
Growth Hormone Receptor ◽  
Expression Profiles ◽  
The Other ◽  
Mrna Levels ◽  
Transcript Levels ◽  
Factor I ◽  
Igf I

Abstract. The goals of this study were to compare the mRNA expression profiles of growth hormone recep tor (GHR) and insulin-like growth factor I (IGF-I) in various tissues of cattle and the semi-wild yak (Datong yak) and to find out whether the mRNA levels of the two genes are correlated. The mRNA levels of GHR and IGF-I in heart, lung, liver, spleen, pancreas, kidney, muscle, mammary gland and ovary of cattle and yak were investigated by using quantitative real-time po ly mer ase chain reaction (PCR). The experiments showed that the transcript levels of the two genes were signif icantly higher in liver (P<0.05) than in the other tissues for both species and that IGF-I levels varied more among tissues (P<0.01) than did GHR levels. The GHR tran script level in pancreas was higher in yak (P<0.05) than in cattle. There was no statistically sig nif i cant difference in IGF-I tran script levels among all the tissues of both bovine groups. Growth hormone receptor and IGF-I transcript levels were positively correlated in mammary gland (P<0.01), lung (P<0.05) and muscle (P<0.05) in yak, negatively correlated in cattle heart (P<0.05) and not correlated in the other tissues. The results indicate that the two genes are reg u lated differently in various tissues under normal physiological conditions in these two bovine species.

Laron syndrome – A case Report

JMS SKIMS ◽  
2017 ◽  
Vol 20 (2) ◽  
pp. 104-106
Author(s):  
Javaid Ahmad Bhat ◽  
Moomin Hussain Bhat ◽  
Hilal Bhat ◽  
Mona Sood ◽  
Shariq Rashid Masoodi
Keyword(s):  
Growth Hormone ◽  
Case Report ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Genetic Disorder ◽  
Female Child ◽  
Receptor Signaling ◽  
Laron Syndrome ◽  
Rare Genetic Disorder ◽  
Igf I

Background : Laron & colleagues (1966) reported a rare genetic disorder in Israliei Jewish sublings which was characterized by insensitivity to growth hormone due to abnormality in growth hormone receptor or post receptor signaling pathway.Case Report: We hereby report a case of a 5 year old female child who presented to us with features similar to Laron syndrome. The diagnosis was made & confirmed by various Lab. investigations like low IGF-I levels and managed accordingly. JMS 2017; 20 (2):104-106  

Growth hormone-binding protein levels: Studies of children with short stature

Metabolism ◽  
1994 ◽  
Vol 43 (3) ◽  
pp. 357-359 ◽  
Author(s):  
Nelly Mauras ◽  
Lena M.S. Carlsson ◽  
Suzanne Murphy ◽  
Thomas J. Merimee
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Binding Protein ◽  
Hormone Binding ◽  
Protein Levels ◽  
Growth Hormone Binding Protein ◽  
Hormone Binding Protein
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