Reduction in circulating IGF-I and hepatic IGF-I mRNA levels after caecal ligation and puncture are associated with differential regulation of hepatic IGF-binding protein-1, -2 and -3 mRNA levels

1996 ◽  
Vol 151 (2) ◽  
pp. 287-292 ◽  
Author(s):  
J Rodríguez-Arnao ◽  
G Yarwood ◽  
C Ferguson ◽  
J Miell ◽  
C J Hinds ◽  
...  

Abstract Sepsis is characterized by a severe shift in metabolism, characterized by low IGF-I levels. We have studied the influence of caecal ligation and puncture (CLP) on the levels of circulating IGF-I and hepatic IGF-I and IGF-binding protein (IGFBP)-1, -2 and -3 mRNA in adult male Wistar rats (n=12) and compared it with sham-operated rats (n=6). In order to exclude anorexia-induced changes we also studied animals pair-fed to both groups. IGF-I levels were measured by RIA. Steady-state hepatic IGF-I, IGFBP-1, IGFBP-2 and IGFBP-3 mRNA levels were measured by Northern blot analysis using specific rat cDNA probes. Food intake averaged 13·0 ± 2·0 g/day in the sham-operated rats fed ad libitum during the study period, with a sharp decline in food intake in the CLP animals (2·3 ± 1·3 g/day). After CLP, there was a significant reduction in circulating IGF-I levels (467·2 ± 50·9 μg/l) compared with sham-operated animals (924·0 ± 75·3 μg/l; P=0·04) or those pair-fed to the CLP rats (612·5 ± 52·9 μg/l; P=0·04). Total hepatic IGF-I mRNA levels were significantly reduced (2·57 ± 0·05 densitometric units (DU)) after CLP compared with the sham-operated group (2·71 ± 0·04; P=0·04), or their pair-fed controls (2·75 ± 0·08 DU; P<0·05). Hepatic IGFBP-3 mRNA levels were lower after CLP (0·37 ± 0·04 DU) than in the sham-operated animals (0·66 ± 0·09 DU; P=0·04) or their pair-fed controls (0·61 ± 0·05 DU; P=0·04). On the other hand, hepatic IGFBP-2 mRNA levels were increased after CLP (0·91 ± 0·11 DU) compared with sham-operated animals (0·28 ± 0·06 DU; P=0·01) or with their pair-fed controls (0·22 ± 0·22; P=0·01), as were hepatic IGFBP-1 mRNA levels (CLP animals 0·95 ± 0·11 DU; sham-operated 0·30 ± 0·04 DU, P=0·01; pair-fed 0·30 ± 0·02 DU, P=0·01). No significant difference between sham-operated animals and their pair-fed controls was observed in circulating IGF-I levels (888·0 ± 109·3 μg/l; P=not significant (N.S.)), hepatic mRNA levels for IGF-I (2·72 ± 0·06 DU; P=N.S), IGFBP-3 (0·71 ± 0·07 DU; P=N.S.), IGFBP-2 (0·25 ± 0·07 DU; P=N.S.) or IGFBP-1 (0·27 ± 0·06 DU; P=N.S.). In summary, after CLP there was a reduction in both circulating and hepatic IGF-I mRNA levels associated with a specific and differential regulation of hepatic IGFBP-1, -2 and -3 mRNA levels. Although we cannot eliminate a possible effect of surgical stress combined with malnutrition, our results suggest that these changes are a specific effect of sepsis rather than simply a result of surgical stress or poor nutrition alone. Journal of Endocrinology (1996) 151, 287–292

2005 ◽  
Vol 185 (3) ◽  
pp. 467-476 ◽  
Author(s):  
Teresa Priego ◽  
Miriam Granado ◽  
Ana Isabel Martín ◽  
Asunción López-Calderón ◽  
María Angeles Villanúa

The aim of this study was to investigate whether glucocorticoid administration had a beneficial effect on serum concentrations of insulin-like growth factor I (IGF-I) and on IGF-binding protein 3 (IGFBP-3) in rats injected with lipopolysaccharide (LPS). Adult male rats were injected with LPS or saline and pretreated with dexamethasone or saline. Dexamethasone administration decreased growth hormone (GH) receptor and IGF-I mRNA levels in the liver of control rats. LPS decreased GH receptor and IGF-I gene expression in the liver of saline-treated rats but not in the liver of dexamethasone-pretreated rats. In the kidney, GH receptor mRNA levels were not modified by dexamethasone or LPS treatment. However, LPS decreased renal IGF-I gene expression and dexamethasone pretreatment prevented this decrease. Serum concentrations of IGF-I were decreased by LPS, and dexamethasone pretreatment attenuated this effect. The gene expression of IGFBP-3 in the liver and kidney and its circulating levels were decreased by LPS. In control rats dexamethasone increased circulating IGFBP-3 and its gene expression in the liver, and decreased the proteolysis of this protein. Dexamethasone pretreatment attenuated the LPS-induced decrease in IGFBP-3 gene expression in the liver and prevented the LPS-induced decrease in IGFBP-3 gene expression in the kidney. Moreover, dexamethasone pretreatment attenuated the LPS-induced decrease in serum concentrations of IGFBP-3 and decreased the LPS-induced IGFBP-3 proteolysis in serum. In conclusion, dexamethasone pretreatment partially attenuates the inhibitory effect of LPS on serum IGF-I by blocking the decrease of its gene expression in the kidney as well as by attenuating the decrease in serum concentrations of IGFBP-3.


1993 ◽  
Vol 138 (3) ◽  
pp. 421-427 ◽  
Author(s):  
I. J. Clarke ◽  
T. P. Fletcher ◽  
C. C. Pomares ◽  
J. H. G. Holmes ◽  
F. Dunshea ◽  
...  

ABSTRACT Three groups of mature rams were maintained on diets of hay, hay+2% lupin or hay+2% cowpea for 11 weeks. Serial blood samples were taken at 15-min intervals for 12 h for the determination of GH and IGF-I content by radioimmunoassay and for IGF-binding protein-3 (IGFBP-3) levels by Western blotting. The rams were killed after 77 days of supplementary feeding and their pituitary glands analysed for content of GH and GH mRNA. Mean plasma GH and baseline GH levels were significantly (P<0·01) decreased in the rams fed lupin and cowpea compared with controls fed hay and GH pulse amplitude was significantly (P<0·001) decreased in the group fed the cowpea diet. The frequency of GH pulses was not significantly altered by either treatment. Plasma concentrations of IGF-I were elevated in rams fed lupin (P<0·001) or cowpea (P<0·05). IGFBP-3 levels were not significantly (P>0·05) altered by either treatment. There were no significant differences in pituitary content of GH mRNA but pituitary content of GH was increased in rams fed lupin (P<0·05) and cowpea (P=0·07). In conclusion, a high-protein diet decreases plasma GH levels and increases IGF-I without changing plasma IGFBP-3 levels in rams. Thus ongoing synthesis of GH, as indicated by the mRNA levels, may cause a build up of GH stores in the pituitary gland. Journal of Endocrinology (1993) 138, 421–427


2003 ◽  
Vol 284 (4) ◽  
pp. C860-C869 ◽  
Author(s):  
Toan-Thang Phan ◽  
Ivor Jiun Lim ◽  
Boon Huat Bay ◽  
Robert Qi ◽  
Michael Thornton Longaker ◽  
...  

Keloids are proliferative dermal growths representing a pathological wound-healing response. We report high proliferation rates in normal (NF) and keloid-derived fibroblasts (KF) cocultured with keloid-derived keratinocytes (KK). IGF binding protein (IGFBP)-3 mRNA and secreted IGFBP-3 in conditioned media were increased in NF cocultured with KK compared with NF but markedly reduced in KF cocultured with KK or normal keratinocytes (NK). IGFBP-2 and IGFBP-4 mRNA levels were elevated, whereas IGFBP-5 mRNA was decreased in KF cocultured with KK or NK. Significant increases in IGFBP-2 and -4 mRNA in KF cocultured with KK did not correlate with protein secretion. Downstream IGF signaling cascade components, phospho-Raf, phospho-MEK1/2, phospho-MAPK, PI-3 kinase, phospho-Akt, and phospho-Elk-1, were elevated in KF cocultured with KK. Addition of recombinant human IGFBP-3 or antibodies against IGF-I or IGF-IR significantly inhibited proliferation of KF. The bioavailability of IGF-I may be related to the levels of IGFBP-3 produced, which in turn influences KF proliferation, suggesting that modulation of IGF-I, IGF-IR, and IGFBP-3, individually or in combination, may represent novel approaches to the treatment of keloids.


2002 ◽  
pp. 729-739 ◽  
Author(s):  
R Rosato ◽  
D Lindenbergh-Kortleve ◽  
J Neck ◽  
S Drop ◽  
G Jahn

OBJECTIVE: Hyperthyroidism in rats produces organ hypertrophy and increases in circulating IGF-I and IGF-binding protein (IGFBP)-3. Chronic treatment with thyroxine (T(4)) during pregnancy advances parturition, blocks lactation and changes several hormone receptors in mammary gland and liver. Since IGFs are implicated in mammary and liver growth and in differentiation, we studied the effects of hyperthyroidism, induced by daily injections of T(4) (0.25 mg/kg). DESIGN AND METHODS: Using quantitative RT-PCR and in situ hybridization, the gene expression of IGF-I, IGF-II and the IGFBPs was determined in mammary gland and liver of rats at estrus and days 7, 14 and 21 of pregnancy (G7, G14, G21), day 1 postpartum (L1) and 3 days after removing the litter (L4). Circulating levels of IGF-I, tri-iodothyronine (T(3)), PRL and GH were measured. RESULTS: T(4) treatment (HT) increased circulating T(3) save on G21, did not change serum IGF-I, increased PRL on G21 and decreased GH on L1. PRL decreased on L1 because of the absence of lactation. Hepatic IGF-I mRNA was low during pregnancy and increased on L4. HT advanced this increase to L1. In controls, liver IGFBP-3 mRNA levels decreased from G14 to G21, whereas IGFBP-4 showed an inverse pattern. HT lowered IGFBP-3 mRNA and increased IGFBP-4. Increases in mammary concentrations of IGF-I, IGFBP-3 and IGFBP-4 mRNAs were seen on G21. HT delayed these peaks to L1. Mammary IGF-II and IGFBP-2 mRNA levels were high on G7 and G14, and fell afterwards, with HT having no effects. IGFBP-5 mRNA decreased during pregnancy and increased on L1. HT increased IGFBP-5 levels in early pregnancy and on L1. IGF-I mRNA localized to connective and epithelial mammary tissue, while IGFBP-2 and IGFBP-5 mRNA was only in epithelial cells. CONCLUSION: These results imply a role for IGF-I, IGFBP-3 and IGFBP-4 in terminal mammary development, while IGF-II and IGFBP-2 may be implicated in early growth. IGFBP-5 has been implicated in mammary apoptosis, and the HT-induced increase may play a role in the premature mammary involution of the HT rats.


2006 ◽  
Vol 16 (2) ◽  
pp. 86-92 ◽  
Author(s):  
Tiffany G. Harris ◽  
Howard D. Strickler ◽  
Herbert Yu ◽  
Michael N. Pollak ◽  
E. Scott Monrad ◽  
...  

2007 ◽  
Vol 92 (9) ◽  
pp. 3660-3666 ◽  
Author(s):  
Iona Cheng ◽  
Katherine DeLellis Henderson ◽  
Christopher A. Haiman ◽  
Laurence N. Kolonel ◽  
Brian E. Henderson ◽  
...  

2012 ◽  
Vol 77 (6) ◽  
pp. 341-350 ◽  
Author(s):  
Eva Landmann ◽  
Barbara Kollerits ◽  
Joachim Gerhard Kreuder ◽  
Werner Friedrich Blum ◽  
Florian Kronenberg ◽  
...  

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