scholarly journals Growth hormone protects against radiotherapy-induced cell death

2002 ◽  
pp. 535-541 ◽  
Author(s):  
O Madrid ◽  
S Varea ◽  
I Sanchez-Perez ◽  
L Gomez-Garcia ◽  
E De Miguel ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cell Death ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Molecular Mechanisms ◽  
Dna Double Strand Breaks ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
Rat Growth

BACKGROUND: In vivo treatment with growth hormone reduces radiation-associated mortality. The molecular mechanisms underlying this effect are unknown. It has been described that increased sensitivity to ionising radiation can be due to defects in machinery involved in detection and/or repair of DNA double-strand breaks. OBJECTIVE: To study the mechanisms involved in growth hormone action on the increased survival in irradiated cells. MATERIALS AND METHODS: CHO-4 cells stably expressing the growth hormone receptor were used. A cell viability assay was carried out to analyse the increase in survival induced by growth hormone in irradiated cells. To investigate whether the DNA repair mechanism could be implicated in this effect we performed DNA reactivation assays using pHIV-LUC and pCMV-betagal plasmids as control. Identical studies were also conducted using the radiomimetic drug, bleomycin. RESULTS: Growth hormone protects CHO-4 cells from bleomycin- and radiation-induced cell death. In pHIV-LUC transfected cells, a time-dependent decrease in luciferase activity was observed after irradiation in the absence of growth hormone. However, cells pretreated with this hormone maintained reporter activity. When cells were transfected with irradiated pHIV-LUC plasmid, only the hormone-treated cells recovered the transcriptional activity. CONCLUSIONS: Growth hormone exerts a radioprotective effect in CHO-4 cells stably transfected with the complementary DNA for the rat growth hormone receptor. The radioprotection is triggered directly by the hormone and it is also observed with bleomycin. The increased survival in response to radiation and bleomycin treatment induced by growth hormone correlates with an enhanced ability of the cells to repair damaged DNA.

scholarly journals Compensatory alterations of insulin signal transduction in liver of growth hormone receptor knockout mice

2000 ◽  
Vol 166 (3) ◽  
pp. 579-590 ◽  
Author(s):  
FP Dominici ◽  
G Arostegui Diaz ◽  
A Bartke ◽  
JJ Kopchick ◽  
D Turyn
Keyword(s):  
Growth Hormone ◽  
Tyrosine Phosphorylation ◽  
Growth Hormone Receptor ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Insulin Signal Transduction ◽  
Increased Sensitivity ◽  
Binding Protein Gene ◽  
Insulin Hypersensitivity

Growth hormone (GH) deficiency is associated with increased sensitivity to insulin, but the molecular mechanisms involved in this association are poorly understood. In the current work, we have examined the consequences of the absence of the biological effects of GH on the first steps of the insulin signaling system in vivo in liver of mice with targeted disruption of the GH receptor/GH binding protein gene (GHR-KO mice). In these animals, circulating insulin concentrations are less than 4 microIU/ml, and glucose concentrations are low, concordant with a state of insulin hypersensitivity. The abundance and tyrosine phosphorylation state of the insulin receptor (IR), the IR substrate-1 (IRS-1), and Shc, the association between IRS-1 and the p85 subunit of phosphatidylinositol (PI) 3-kinase, the IRS-1- and the phosphotyrosine-associated PI 3-kinase in liver were examined. We found that, in liver of GHR-KO mice, the lack of GHR and GH eff! ects is associated with: (1) increased IR abundance, (2) increased insulin-stimulated IR tyrosine phosphorylation, (3) normal efficiency of IRS-1 and Shc tyrosine phosphorylation and (4) normal activation of PI 3-kinase by insulin. These alterations could represent an adaptation to the low insulin concentrations displayed by these animals, and may account for their increased insulin sensitivity.

scholarly journals Small glutamine-rich tetratricopeptide repeat-containing protein (SGT) interacts with the ubiquitin-dependent endocytosis (UbE) motif of the growth hormone receptor

2003 ◽  
Vol 373 (3) ◽  
pp. 855-863 ◽  
Author(s):  
Julia A. SCHANTL ◽  
Marcel ROZA ◽  
Ad P. De JONG ◽  
Ger J. STROUS
Keyword(s):  
Growth Hormone ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Tetratricopeptide Repeat ◽  
Glutathione S Transferase ◽  
Binding Studies ◽  
Interacting Protein ◽  
System A ◽  
Pulldown Assay

Endocytosis of the growth hormone receptor (GHR) is regulated by the ubiquitin-conjugating system. A cytosolic 10 amino acid motif, referred to as the ubiquitin-dependent endocytosis (UbE) motif, is involved in the ubiquitination as well as in the endocytosis of the receptor. Proteins that are implicated in one of these processes have not been identified so far. Using a glutathione S-transferase (GST)-pulldown assay with a GST fusion protein encompassing the UbE motif of the GHR, a 35 kDa protein was purified. The protein was identified by MS as small glutamine-rich tetratricopeptide repeat (TPR)-containing protein (SGT). We found that GHR interacts with SGT. In vivo, both the precursor and the mature form of the receptor interacted with SGT. Inactivation of the ubiquitin-conjugating system did not affect the GHR–SGT interaction. Binding studies showed that the first TPR motif of SGT interacts with the UbE motif of the GHR. Taken together, these data show that SGT is a GHR-interacting protein, which binds independent of the ubiquitin-conjugating system.

Localization and Regulation of the Growth Hormone Receptor and Growth Hormone-Binding Protein in the Rat Growth Plate

2002 ◽  
Vol 17 (8) ◽  
pp. 1408-1419 ◽  
Author(s):  
Evelien F. Gevers ◽  
Bram C. J. Van Der Eerden ◽  
Marcel Karperien ◽  
Anton K. Raap ◽  
Iain C. A. F. Robinson ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Plate ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Binding Protein ◽  
Hormone Binding ◽  
Growth Hormone Binding Protein ◽  
Rat Growth ◽  
Hormone Binding Protein
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