Growth hormone promotes early initiation of hepatocyte growth factor gene expression in the liver of hypophysectomized rats after partial hepatectomy

1992 ◽  
Vol 135 (1) ◽  
pp. 59-67 ◽  
Author(s):  
S. Ekberg ◽  
M. Luther ◽  
T. Nakamura ◽  
J.-O. Jansson
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Dna Synthesis ◽  
Partial Hepatectomy ◽  
Hepatic Regeneration ◽  
Mrna Levels ◽  
Gh Treatment ◽  
Igf I ◽  
Hypophysectomized Rats ◽  
Hepatocyte Growth

ABSTRACT GH accelerates hepatic regeneration in the rat. Hepatocyte growth factor (HGF), a potent hepatocyte mitogen in vitro, is considered to be a major regulator of hepatic regeneration. In the present study, the effects of GH and insulin-like growth factor-I (IGF-I) on HGF gene expression in regenerating rat liver was investigated. In hypophysectomized rats treated with GH, hepatic HGF mRNA levels were increased 3 h after partial hepatectomy and reached peak levels after 5 h. In rats with intact pituitaries and in hypophysectomized rats not given GH treatment, HGF mRNA levels in liver were unchanged during the first 5 h following hepatectomy and reached peak levels after 10-18 h. DNA synthesis in the liver of GH-treated rats increased from low levels 10 h after hepatectomy to peak levels after 18 h. In rats without GH treatment the synthesis of DNA was still low 18 h after hepatectomy and was increased after 26 h. Treatment of hypophysectomized rats with IGF-I promoted increases in hepatic HGF mRNA levels and DNA synthesis 3·5 h and 15 h after hepatectomy respectively. HGF mRNA levels were constantly lower after sham-hepatectomy than after partial hepatectomy. In summary, in hypophysectomized rats the responses of hepatic HGF gene expression and DNA synthesis to partial hepatectomy were both accelerated by treatment with GH or IGF-I. Journal of Endocrinology (1992) 135, 59–67

Hepatocellular expression of glucose-6-phosphatase is unaltered during hepatic regeneration

1998 ◽  
Vol 275 (4) ◽  
pp. G717-G722 ◽  
Author(s):  
Wisam F. Zakko ◽  
Carl L. Berg ◽  
John L. Gollan ◽  
Richard M. Green
Keyword(s):  
Gene Expression ◽  
Enzyme Activity ◽  
Protein Expression ◽  
Partial Hepatectomy ◽  
Initial Phase ◽  
Physiological Function ◽  
Liver Homogenate ◽  
Hepatic Regeneration ◽  
Mrna Levels ◽  
Microsomal Enzyme

Gluconeogenesis and glycogenolysis are essential hepatic functions required for glucose homeostasis. During the initial phase of hepatic regeneration, the immediate-early genes (IEG) are rapidly expressed, and the IEG RL-1 encodes for glucose-6-phosphatase (G-6- Pase). G-6- Pase is a microsomal enzyme essential for gluconeogenesis and glycogenolysis. This study employs a partial-hepatectomy model to examine the expression and activity of G-6- Pase. After partial hepatectomy, rat hepatic G-6- Pase gene expression is transcriptionally regulated, and mRNA levels are increased ≈30-fold. However, in contrast to this rapid gene induction, microsomal enzyme activity is unchanged after partial hepatectomy. Western blotting demonstrates that microsomal G-6- Pase protein expression is also unchanged after partial hepatectomy, and similar results are also noted in whole liver homogenate. Thus, despite marked induction in gene expression of the IEG G-6- Pase after partial hepatectomy, protein expression and enzyme activity remain unchanged. These data indicate that, although this hepatocyte IEG is transcriptionally regulated, the physiologically important level of regulation is posttranscriptional. This highlights the importance of correlating gene expression of IEG with protein expression and physiological function.

Activation of insulin-like growth factor gene expression during work-induced skeletal muscle growth

1990 ◽  
Vol 259 (1) ◽  
pp. E89-E95 ◽  
Author(s):  
D. L. DeVol ◽  
P. Rotwein ◽  
J. L. Sadow ◽  
J. Novakofski ◽  
P. J. Bechtel
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Growth ◽  
Experimental Period ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Muscle Weight ◽  
Skeletal Muscle Growth ◽  
Igf I

We have investigated the hypothesis that there is local regulation of insulin-like growth factor (IGF) gene expression during skeletal muscle growth. Compensatory hypertrophy was induced in the soleus, a predominantly slow-twitch muscle, and plantaris, a fast-twitch muscle, in 11- to 12-wk-old female Wistar rats by unilateral cutting of the distal gastrocnemius tendon. Animals were killed 2, 4, or 8 days later, and muscles of the nonoperated leg served as controls. Muscle weight increased throughout the experimental period, reaching 127% (soleus) or 122% (plantaris) of control values by day 8. In both growing muscles, IGF-I mRNA, quantitated by a solution-hybridization nuclease-protection assay, rose by nearly threefold on day 2 and remained elevated throughout the experimental period. IGF-II mRNA levels also increased over controls. A more dramatic response was seen in hypophysectomized rats, where IGF-I mRNA levels rose by 8- to 13-fold, IGF-II values by 3- to 7-fold, and muscle mass increased on day 8 to 149% (soleus) or 133% (plantaris) of the control contralateral limb. These results indicate that signals propagated during muscle hypertrophy enhance the expression of both IGF genes, that modulation of IGF-I mRNA levels can occur in the absence of growth hormone, and that locally produced IGF-I and IGF-II may play a role in skeletal muscle growth.

Increased insulin-like growth factor binding protein-4 expression after partial hepatectomy in the rat

2000 ◽  
Vol 278 (3) ◽  
pp. G384-G389 ◽  
Author(s):  
Ilaria Demori ◽  
Sara Balocco ◽  
Adriana Voci ◽  
Emilia Fugassa
Keyword(s):  
Growth Factor ◽  
Cell Growth ◽  
Partial Hepatectomy ◽  
Transcript Abundance ◽  
Early Gene ◽  
Hepatic Regeneration ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Rat Serum

The insulin-like growth factor (IGF) binding proteins (IGFBPs) are important regulators of cell growth produced by different tissues. The IGFBPs regulate cell growth by modulating the activity and bioavailability of IGFs. The evidence that IGFBP-1 is a liver-specific immediate-early gene highly induced after 70% partial hepatectomy (PHx) suggests a role for the IGF-IGFBP system in hepatic regeneration. In this work we analyzed the effect of PHx on the expression of IGFBP-4, which is highly produced by the liver and very abundant in rat serum. Our results show a marked increase in hepatic IGFBP-4 mRNA levels 6–12 h after PHx and no significant change in sham-operated control animals. A parallel rise in IGFBP-4 transcript abundance was observed in the kidneys of PHx rats but not in sham-operated animals. Moreover, ligand blot analysis demonstrated that serum IGFBP-4 levels began to increase 12–24 h after surgery, consistent with the rise in the corresponding mRNA. This enhancement in IGFBP-4 production after PHx could be part of a fine regulatory mechanism to modulate IGF activity during liver regeneration.

scholarly journals Inhibition by Interleukin-1β and Tumor Necrosis Factor-α of the Insulin-Like Growth Factor I Messenger Ribonucleic Acid Response to Growth Hormone in Rat Hepatocyte Primary Culture*

Endocrinology ◽  
1997 ◽  
Vol 138 (3) ◽  
pp. 1078-1084 ◽  
Author(s):  
Jean-Paul Thissen ◽  
Josiane Verniers
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Mrna Levels ◽  
Factor I ◽  
Tnf Α ◽  
Igf I ◽  
Necrosis Factor ◽  
I Gene

Abstract The cytokines are the putative mediators of the catabolic reaction that accompanies infection and trauma. Evidence suggests that their catabolic actions are indirect and potentially mediated through changes in hormonal axis such as the hypothalamo-pituitary-adrenal axis. Insulin-like growth factor I (IGF-I) is a GH-dependent growth factor that regulates the protein metabolism. To determine whether cytokines can directly inhibit the production of IGF-I by the liver, we investigated the regulation of IGF-I gene expression by interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α (10 ng/ml) in a model of rat primary cultured hepatocytes. Hepatocytes were isolated by liver collagenase perfusion and cultured on Matrigel 48 h before experiments. Each experiment was performed in at least three different animals. In the absence of GH, IL-1β and TNF-α did not affect the IGF-I messenger RNA (mRNA) basal levels, whereas IL-6 increased it by a factor of 2.5 after 24 h (P < 0.05). GH (500 ng/ml) alone stimulated the IGF-I gene expression markedly (5- to 10-fold increase) after 24 h (P < 0.001). IL-1β, and TNF-α to a lesser extent, dramatically inhibited the IGF-I mRNA response to GH (IL-1β: −82%, P < 0.001 and TNF-α: −47%, P < 0.01). The half-maximal inhibition of the IGF-I mRNA response to GH was observed for a concentration of IL-1β between 0.1 and 1 ng/ml. Moreover, IL-1β abolished the IL-6-induced IGF-I mRNA response. In contrast, IL-6 did not impair the IGF-I mRNA response to GH. To determine the potential role of the GH receptor (GHR) and the GH-binding protein (GHBP) in this GH resistance, we assessed the GHR and GHBP mRNAs response to these cytokines. GH alone did not affect the GHR/GHBP mRNA levels. IL-1β markedly decreased the GHR and GHBP mRNA levels (respectively, −68% and −60%, P < 0.05). Neither TNF-α nor IL-6 affected the GHR/GHBP gene expression. In conclusion, our results show that IL-1β, and TNF-α to a lesser extent, blunt the IGF-I mRNA response to GH. The resistance to GH induced by IL-1β might be mediated by a decrease of GH receptors, as suggested by the marked reduction of GHR mRNA. These findings suggest that decreased circulating IGF-I, in response to infection and trauma, may be caused by a direct effect of cytokines at the hepatocyte level.

Regulation of insulin-like growth factor-I and growth hormone receptor gene expression by diabetes and nutritional state in rat tissues

1989 ◽  
Vol 122 (3) ◽  
pp. 651-656 ◽  
Author(s):  
K. E. Bornfeldt ◽  
H. J. Arnqvist ◽  
B. Enberg ◽  
L. S. Mathews ◽  
G. Norstedt
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Receptor Gene ◽  
Mrna Levels ◽  
Factor I ◽  
Receptor Mrna ◽  
Gh Receptor ◽  
Igf I ◽  
Receptor Gene Expression ◽  
Different Tissues

ABSTRACT Insulin-like growth factor-I (IGF-I) mRNA and GH receptor mRNA levels were analysed in different tissues from rats made diabetic with streptozotocin, fasted rats and rats fed with a protein-reduced diet. Diabetes decreased IGF-I mRNA levels in liver, heart, diaphragm, kidney and aorta, but not in brain. GH receptor mRNA levels were decreased in heart and diaphragm, but not in liver and kidney. Fasting decreased IGF-I mRNA in all tissues studied except brain, and decreased GH receptor mRNA in liver, heart and diaphragm, but not in kidney. A protein-reduced diet decreased hepatic IGF-I mRNA levels but did not significantly affect other tissues, while GH receptor mRNA levels were reduced in liver and diaphragm. In conclusion, both diabetes and limited nutrition affected IGF-I and GH receptor mRNA in different tissues, but the two mRNAs were not co-ordinately regulated in all tissues studied. While reduced GH receptor gene expression may thus be responsible for decreased IGF-I gene expression in some states and tissues, additional regulatory mechanisms may be of importance. Journal of Endocrinology (1989) 122, 651–656

scholarly journals Metabolic hormones regulate insulin-like growth factor binding protein-1 mRNA levels in primary cultured salmon hepatocytes; lack of inhibition by insulin

2006 ◽  
Vol 191 (2) ◽  
pp. 379-386 ◽  
Author(s):  
A L Pierce ◽  
M Shimizu ◽  
L Felli ◽  
P Swanson ◽  
W W Dickhoff
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Hormonal Regulation ◽  
Growth And Development ◽  
Mrna Levels ◽  
Igf Binding Proteins ◽  
Metabolic Hormones ◽  
Igf I ◽  
Igf Binding

IGF-binding proteins (IGFBPs) modulate the effects of the IGFs, major stimulators of vertebrate growth and development. In mammals, IGFBP-1 inhibits the actions of IGF-I. Rapid increases in circulating IGFBP-1 occur during catabolic states. Insulin and glucocorticoids are the primary regulators of circulating IGFBP-1 in mammals. Insulin inhibits and glucocorticoids stimulate hepatocyte IGFBP-1 gene expression and production. A 22 kDa IGFBP in salmon blood also increases during catabolic states and has recently been identified as an IGFBP-1 homolog. We examined the hormonal regulation of salmon IGFBP-1 mRNA levels and protein secretion in primary cultured salmon hepatocytes. The glucocorticoid agonist dexamethasone progressively increased hepatocyte IGFBP-1 mRNA levels (eightfold) and medium IGFBP-1 immunoreactivity over concentrations comparable with stressed circulating cortisol levels (10−9–10−6 M). GH progressively reduced IGFBP-1 mRNA levels (0.3-fold) and medium IGFBP-1 immunoreactivity over physiological concentrations (5 × 10−11–5 × 10−9 M). Unexpectedly, insulin slightly increased hepatocyte IGFBP-1 mRNA (1.4-fold) and did not change medium IGFBP-1 immunoreactivity over physiological concentrations and above (10−9–10−6 M). Triiodothyronine had no effect on hepatocyte IGFBP-1 mRNA, whereas glucagon increased IGFBP-1 mRNA (2.2-fold) at supraphysiological concentrations (10−6 M). This study suggests that the major inhibitory role of insulin in the regulation of liver IGFBP-1 production in mammals is not found in salmon. However, regulation of salmon liver IGFBP-1 production by other metabolic hormones is similar to what is found in mammals.

Interaction of angiotensin II and the insulin-like growth factor system in vascular smooth muscle cells

1999 ◽  
Vol 277 (2) ◽  
pp. H499-H507 ◽  
Author(s):  
Thomas Gustafsson ◽  
Peter Andersson ◽  
Yun Chen ◽  
Jan Olof Magnusson ◽  
Hans J. Arnqvist
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Dna Synthesis ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Ang Ii ◽  
Igf I

We studied the effects and interactions of ANG II and the insulin-like growth factor (IGF) system in cultured rat aortic smooth muscle cells. ANG II (1 μM) and IGF-I (10 nM) stimulated both DNA and protein synthesis. The effects of the two peptides in combination were additive or more than additive. The AT1 receptor antagonist losartan (10 and 100 μM) blocked their synergistic effect on DNA synthesis. IGF binding protein (IGFBP)-1 inhibited the effect of IGF-I but not that of ANG II on DNA synthesis. IGF-I stimulated gene expression of IGFBP-2 and IGFBP-4. ANG II decreased IGF-I, IGFBP-2, and IGFBP-4 transcripts but increased the IGF-I receptor transcript. IGF-I and ANG II in combination had similar effects on gene expression as ANG II alone. The IGFBP-2 and IGFBP-4 peptides could be detected in the conditioned medium. Our results show that ANG II and IGF-I have synergistic effects on vascular smooth muscle cells and that they interact in several ways.

scholarly journals FoxO1 is not a key transcription factor in the regulation of myostatin (mstn-1a and mstn-1b) gene expression in trout myotubes

2011 ◽  
Vol 301 (1) ◽  
pp. R97-R104 ◽  
Author(s):  
Iban Seiliez ◽  
Nathalie Sabin ◽  
Jean-Charles Gabillard
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Growth Factor ◽  
Nuclear Translocation ◽  
Protein Activity ◽  
Gh Treatment ◽  
Its Gene ◽  
Igf I ◽  
The Relationship

In mammals, much evidence has demonstrated the important role of myostatin (MSTN) in regulating muscle mass and identified the transcription factor forkhead box O (FoxO) 1 as a key regulator of its gene expression during atrophy. However, in trout, food deprivation leads to muscle atrophy without an increase of the expression of mstn genes in the muscle. We therefore studied the relationship between FoxO1 activity and the expression of both mstn genes ( mstn1a and mstn1b) in primary culture of trout myotubes. To this aim, two complementary studies were undertaken. In the former, FoxO1 protein activity was modified with insulin-like growth factor-I (IGF-I) treatment, and the consequences on the expression of both mstn genes were monitored. In the second experiment, the expression of both studied genes was modified with growth hormone (GH) treatment, and the activation of FoxO1 protein was investigated. We found that IGF-I induced the phosphorylation of FoxO1 and FoxO4. Moreover, under IGF-I stimulation, FoxO1 was no longer localized in the nucleus, indicating that this growth factor inhibited FoxO1 activity. However, IGF-I treatment had no effect on mstn1a and mstn1b expression, suggesting that FoxO1 would not regulate the expression of mstn genes in trout myotubes. Furthermore, the treatment of myotubes with GH decreased the expression of both mstn genes but has no effect on the phosphorylation of FoxO1, FoxO3, and FoxO4 nor on the nuclear translocation of FoxO1. Altogether, our results showed that mstn1a and mstn1b expressions were not associated with FoxO activity, indicating that FoxO1 is likely not a key regulator of mstn genes in trout myotubes.

scholarly journals Vitamin D analogue EB1089-induced prostate regression is associated with increased gene expression of insulin-like growth factor binding proteins

1999 ◽  
Vol 160 (2) ◽  
pp. 223-229 ◽  
Author(s):  
T Nickerson ◽  
H Huynh
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Vitamin D ◽  
Growth Factor ◽  
Binding Proteins ◽  
Ventral Prostate ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Normal Prostate ◽  
Igf I

Vitamin D analogues have an antiproliferative effect on prostate cancer cells in vitro and thus have been proposed as candidates for chemoprevention of prostate cancer. Insulin-like growth factor (IGF)-I has been shown to protect cells from apoptosis and plays an essential role in normal prostate physiology. We have studied the effects of the 1,25-dihydroxyvitamin D3 analogue EB1089 on the IGF system in the prostate in vivo. Treatment of rats with EB1089 for 14 days caused a 25% decrease in ventral prostate weight. Apoptosis was detected in prostate sections of EB1089-treated rats by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay and histologic examination of hematoxylin/eosin stained tissue sections indicated that secretory epithelial cells were flattened, a characteristic of cells undergoing pressure-induced atrophy. Ventral prostate regression was associated with 15- to 25-fold increases in gene expression of IGF-binding proteins (IGFBPs)-2,-3,-4 and -5. We also observed a 40-fold increase in prostatic IGF-I mRNA levels in response to EB1089. Although we have previously shown that castration of rats leads to upregulation of IGFBPs in the ventral prostate, EB1089 treatment had no effect on serum levels of dihydrotestosterone or free testosterone. These results suggest that prostate regression induced by EB1089 may be related to alterations in availability of IGF-I as a result of increased production of IGFBPs.

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