IGF-binding protein-2 is induced during development of urinary bladder hypertrophy in the diabetic rat

1997 ◽  
Vol 272 (2) ◽  
pp. E297-E303 ◽  
Author(s):  
Y. Chen ◽  
B. Gustafsson ◽  
H. J. Arnqvist
Keyword(s):  
Growth Factor ◽  
Urinary Bladder ◽  
Messenger Rna ◽  
Diabetic Rat ◽  
Insulin Like Growth Factor ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Streptozotocin Induced Diabetes ◽  
Wet Weight

Because the locally produced insulin-like growth factor-binding proteins (IGFBP) may influence bladder hypertrophy, either directly or by their interaction with insulin-like growth factor I (IGF-I), we studied the IGF system during the development of urinary bladder hypertrophy in rats with streptozotocin-induced diabetes. Messenger RNA for IGF-I, IGFBP-2, and IGFBP-4 was determined by solution hybridization. The bladder wet weight was elevated after 7 days. DNA synthesis was increased and peaked at 2 days, whereas DNA content per bladder wet weight was decreased by 7 days. The IGF-I mRNA did not change during the first 7 days and then decreased, and IGFBP-4 mRNA was increased transiently on day 7. On the other hand, IGFBP-2 mRNA was significantly increased after 1 day (2-fold), peaked by 7 days (6.4-fold), and then declined to approximately 50% above control at the end of experiment. This was associated with an increased IGFBP-2 protein content. Our results suggest that both stretching of the bladder due to diuresis and the diabetic state contribute to changes of the IGF system in the hypertrophying bladder.

Increase in insulin-like growth factor I in hypertrophying smooth muscle

1994 ◽  
Vol 266 (2) ◽  
pp. E224-E229 ◽  
Author(s):  
Y. Chen ◽  
K. E. Bornfeldt ◽  
A. Arner ◽  
E. Jennische ◽  
U. Malmqvist ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Portal Vein ◽  
Muscle Hypertrophy ◽  
Insulin Like Growth Factor ◽  
Sprague Dawley ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Wet Weight

The present study focuses on the role of the insulin-like growth factor (IGF) system in the development of smooth muscle hypertrophy. Hypertrophy was initiated by partial ligation of portal vein or urethra in female Sprague-Dawley rats weighing approximately 220 g. Levels of mRNA were analyzed by solution hybridization. Seven days after ligation, the wet weight of the portal vein was increased about threefold and the concentration of IGF-I mRNA was increased fourfold. The bladder wet weight was increased twofold 3 days after ligation and fourfold 10 days after ligation. IGF-I mRNA in the bladder was elevated 3-fold after 3 days and 2.5-fold after 10 days, whereas IGF binding protein 2 mRNA was increased approximately 2-fold after 3 days and 5-fold after 10 days. IGF-I receptor mRNA in the hypertrophying bladder remained unchanged. Increased levels of IGF-I were demonstrated with immunohistochemistry in both hypertrophying portal vein and urinary bladder. The results show a specific increase in IGF-I mRNA as well as an increased IGF-I immunoreactivity during hypertrophy of smooth muscle, which suggests that the local IGF-system may play a role in smooth muscle hypertrophy.

scholarly journals Insulin-like growth factors-I and -II and insulin-like growth factor-binding protein-2 in dominant equine follicles during spring transition and the ovulatory season

Reproduction ◽  
2004 ◽  
Vol 128 (3) ◽  
pp. 321-329 ◽  
Author(s):  
E D Watson ◽  
S-E Bae ◽  
R Thomassen ◽  
S R M Thomson ◽  
K Woad ◽  
...  
Keyword(s):  
Growth Factor ◽  
Breeding Season ◽  
Messenger Rna ◽  
Threshold Level ◽  
Insulin Like Growth Factor ◽  
Igf System ◽  
Preovulatory Follicles ◽  
Igf I ◽  
Cyclical Growth ◽  
Somatotrophic Axis

The period between seasonal anoestrus and cyclicity is characterized in many mares by cyclical growth and regression of large dominant follicles. The insulin-like growth factor (IGF) system plays a key role in follicular growth and regression; therefore, we hypothesized that changes in the IGF system and its binding proteins would modulate onset of cyclicity in mares. Ovaries were obtained from pony mares on the day after detection of an actively growing 30 mm transitional anovulatory follicle, and also at the second or third oestrus of the breeding season on the day after the preovulatory follicle reached 30 mm in diameter. Size of dominant follicles at the time of removal was similar in transition (32 ± 0.8 mm) and at oestrus (34 ± 0.6 mm). IGF-I mRNA was present in granulosa cells, with low thecal expression, whereas IGF-II mRNA was confined to the theca layer. Expression of IGF-I and -II mRNAs, and intrafollicular concentrations of oestradiol, were lower (P < 0.01; paired t test) in transitional anovulatory follicles than in preovulatory follicles. Messenger RNA encoding IGFBP-2 was present in both theca and granulosa layers. Steady-state concentrations of mRNA encoding IGFBP-2 mRNA increased (P < 0.001) in theca in preovulatory follicles. Intrafollicular concentrations of IGFBP-2 were higher (P < 0.001) in transitional than in preovulatory follicles. The similarity in circulating concentrations of IGF-I in transitional and cyclic mares, suggested that the somatotrophic axis is not involved in transition from anovulatory to ovulatory cycles. The results suggest that the increased expression of IGF-I and -II mRNAs in preovulatory follicles, along with the decrease in IGFBP-2 concentrations, could increase the bioavailability of intrafollicular IGF in large follicles during the breeding season, and support our hypothesis that intrafollicular IGF bioavailability must exceed a threshold level before ovulation can occur.

Expression of the insulin-like growth factor system in the hypokalemic rat kidney

1997 ◽  
Vol 272 (5) ◽  
pp. F661-F667 ◽  
Author(s):  
R. M. Rohan ◽  
T. G. Unterman ◽  
L. Liu ◽  
M. K. Hise
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Insulin Like Growth Factor ◽  
Distal Nephron ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein

We studied the renal expression of the insulin-like growth factor (IGF) system to gain a better perspective of its potential role in the hyperplastic adaptation of the distal nephron to potassium deficiency. Rats were pair fed 1% or 0.002% potassium diets for periods up to 10 days. IGF-I mRNA was diminished in potassium-deficient rats within 4 days, whereas mRNA for IGF binding protein-1 (IGFBP-1), a collecting duct-associated protein, was increased by day 7. At day 10 mRNA for IGFBP-1 in potassium-deficient animals averaged 2.07 +/- 0.53 (mean +/- SD, relative densitometry units) compared with 0.89 +/- 0.26 in control rats (n = 4, P = 0.002). Conversely, IGFBP-3, a binding protein whose mRNA has been localized to the interstitial compartment, averaged 2.40 +/- 0.02 in potassium-deficient rats and 4.77 +/- 0.05 in controls (n = 4, P < 0.03) at day 10 of treatment. Immunohistochemistry performed using a specific IGFBP-1 antibody revealed hyperplasia of distal nephron segments along with an increase in IGFBP-1 in potassium-depleted rats. These data suggest that IGFBP-1 may play an important role in the control of cellular adaptations in the hypokalemic rat kidney either directly by influencing cell migration or indirectly by localizing IGF-I to the distal nephron.

Regulation of insulin-like growth factor (IGF)-I mRNA and peptide and IGF-binding proteins by interleukin-1

1996 ◽  
Vol 270 (3) ◽  
pp. R621-R629 ◽  
Author(s):  
J. Fan ◽  
M. M. Wojnar ◽  
M. Theodorakis ◽  
C. H. Lang
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Fiber Type ◽  
Interleukin 1 ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Ru 486 ◽  
Igf System ◽  
Igf I ◽  
Igf Binding

The purpose of the present study was to determine whether interleukin (IL)-1 would alter the insulin-like growth factor (IGF) system in rats and whether this change was mediated by glucocorticoids. The IGF-I concentration was decreased in plasma (32%), liver (35%), skeletal muscle (40-50% depending on fiber type), pituitary (36%), and brain (52%), and increased in kidney (73%) 6 h after intravenous injection of IL-1 beta. IL-1 beta also decreased IGF-I mRNA levels in liver and muscle and increased expression in kidney. These changes were associated with a > 2.5-fold elevation in plasma corticosterone levels. Pretreatment of rats with the glucocorticoid receptor antagonist RU-486 prevented the IL-1 beta-induced decrease in plasma and liver IGF-I concentration and the reduction in hepatic IGF-I mRNA expression. In contrast, RU-486 did not significantly attenuate the fall in IGF-I content in skeletal muscle, heart, brain, or pituitary or the increase in IGF-I observed in kidney after IL-1 beta. Furthermore, pretreatment with RU-486 did not completely prevent the IL-1 beta-induced decrease in IGF-I mRNA in skeletal muscle. The concentration of both IGF-binding protein (BP)-1 and BP-2 was increased in plasma, liver, and muscle in response to IL-1 beta, and these changes were also not prevented by RU-486. These results indicate that the inflammatory cytokine IL-1 beta is capable of influencing multiple components of the IGF system. Whereas the enhanced endogenous production of glucocorticoids appears to mediate the IL-1 beta-induced decrease in IGF-I synthesis in liver, the changes in IGF-I content observed in other tissues and the increase in IGFBP-1 and IGFBP-2 appear to be largely glucocorticoid independent.

The insulin-like growth factor system in the circulation of patients with viral infections

2004 ◽  
Vol 42 (10) ◽  
Author(s):  
Ivona Baričević ◽  
Olgica Nedić ◽  
Judith Anna Nikolić ◽  
Jasminka Nedeljković
Keyword(s):  
Growth Factor ◽  
Viral Infections ◽  
Serum Cortisol ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Ligand Affinity ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Simplex Virus

AbstractThe insulin-like growth factor (IGF) system was examined in the circulation of patients with viral infections (herpes simplex virus, HSV; cytomegalovirus, CMV; rotavirus, RV and adenovirus, AV). The serum concentrations of IGF-I, IGF-II and cortisol were measured by radioimmunoassay, while IGF-binding proteins (IGFBPs) were characterised by ligand-affinity blotting. Although both IGF-I and IGF-II concentrations were significantly lower in patients with viral infections (p < 0.05) than in healthy persons, the IGF-II/IGF-I ratio was increased (p < 0.05). No correlation between the concentration of IGF-I and IGF-II and the intensity of the antibody response to infection was observed. Ligand-affinity blotting demonstrated decreased amounts of IGFBP-3 (patients with HSV, CMV, AV and some patients with RV), increased IGFBP-2 (some patients with HSV and RV) and IGFBP-1 (patients with RV). Serum cortisol was significantly elevated (p < 0.05) in patients infected with HSV, CMV and RV. The alterations observed can be interpreted as induction of the hypothalamic-pituitary-adrenal axis and suppression of the growth hormone (GH)/IGF axis under the influence of viral infection.

scholarly journals Overexpression of Insulin-Like Growth Factor-Binding Protein-4 (IGFBP-4) in Smooth Muscle Cells of Transgenic Mice through a Smooth Muscle α-Actin-IGFBP-4 Fusion Gene Induces Smooth Muscle Hypoplasia

Endocrinology ◽  
1998 ◽  
Vol 139 (5) ◽  
pp. 2605-2614 ◽  
Author(s):  
Jianwei Wang ◽  
Wen Niu ◽  
David P. Witte ◽  
Steven D. Chernausek ◽  
Yuri E. Nikiforov ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Messenger Rna ◽  
Transgene Expression ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Wet Weight

Abstract Insulin-like growth factor I (IGF-I) has been postulated to function as a smooth muscle cell (SMC) mitogen and to play a role in the pathogenesis of bladder hypertrophy, estrogen-induced uterine growth, and restenosis after arterial angioplasty. IGF-binding protein-4 (IGFBP-4) inhibits IGF-I action in vitro and is the most abundant IGFBP in the rodent arterial wall. To explore the function of this binding protein in vivo, transgenic mouse lines were developed harboring fusion genes consisting of a rat IGFBP-4 complementary DNA cloned downstream of either a −724 bp fragment of the mouse smooth muscle α-actin 5′-flanking region (SMP2-BP-4) or− 1074 bp, 63 bp of 5′-untranslated region, and 2.5 kb of intron 1 of smooth muscle α-actin (SMP8-BP-4). SMP2-BP-4 mice expressed low levels of the exogenous IGFBP-4 messenger RNA (mRNA), which was not specifically targeted to SMC-rich tissue environments, and were therefore not analyzed further. Six SMP8-BP-4 transgenic lines derived from separate founders were characterized. Mating of hemizygous SMP8-BP-4 mice with controls produced about 50% transgenic offspring, with equal sex distribution. Expression of IGFBP-4 mRNA in nontransgenic littermates was maximal in liver and kidney. By contrast, transgenic IGFBP-4 mRNA expression, distinguished because of a smaller transcript size, was confined to SMC-containing tissues, with the following hierarchy: bladder &gt; aorta &gt; stomach = uterus. There was no transgene expression in skeletal muscle, brain, or cardiac myocytes. The abundance of IGFBP-4 measured by Western ligand blotting or by immunoblotting, was 8- to 10-fold higher in aorta and bladder of SMP8-BP-4 mice than in their nontransgenic littermates, with no change in plasma IGFBP-4 levels. Transgenic mice exhibited a significant reduction in wet weight of SMC-rich tissues, including bladder, intestine, aorta, uterus, and stomach, with no change in total body or carcass weight. In situ hybridization showed that transgene expression was targeted exclusively to the muscular layers of the arteries, veins, bladder, ureter, stomach, intestine, and uterus. Overexpression of IGFBP-4 was associated with SMC hypoplasia, a reciprocal phenotype to that of transgenic mice overexpressing IGF-I under control of the same promoter (SMP8-IGF-I). Double transgenic mice derived from mating SMP8-BP-4 with SMP8-IGF-I animals showed a modest decrease in wet weight at selected SMC tissues. Although we cannot exclude that the effects of IGFBP-4 may be IGF independent, these data suggest that IGFBP-4 is a functional antagonist of IGF-I action on SMC in vivo.

Acute alterations in growth hormone-insulin-like growth factor axis in humans injected with endotoxin

1997 ◽  
Vol 273 (1) ◽  
pp. R371-R378 ◽  
Author(s):  
C. H. Lang ◽  
V. Pollard ◽  
J. Fan ◽  
L. D. Traber ◽  
D. L. Traber ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Maximal Increase ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Acute Changes ◽  
Transient Elevation ◽  
Igf Binding Protein

The purpose of the present study was to characterize the acute changes in the insulin-like growth factor (IGF) system in humans after administration of endotoxin (lipopolysaccharide; LPS). Escherichia coli LPS (4 ng/kg) was injected intravenously into healthy adults, and serial blood samples were collected for the next 5 h; subjects injected with saline served as time-matched controls. LPS administration resulted in a gradual decrease in the total extractable IGF-I concentration, which was reduced by approximately 20% over the final 2 h of the experiment; levels of free IGF-I were not significantly altered. LPS also produced a marked but transient elevation in growth hormone (GH) concentration. IGF-binding protein (BP)-1 levels were elevated more than fivefold 2 h after LPS injection, and thereafter levels gradually returned toward baseline. IGFBP-2 concentration also increased after LPS injection, but the maximal increase (approximately 50% above basal) was observed during the final 2 h of the protocol. In contrast, IGFBP-3 levels did not vary over the period examined in response to LPS, and there was no apparent increase in number of BP-3 proteolytic fragments. Cortisol levels were increased early and remained two- to threefold above baseline throughout the protocol. No significant alterations in serum concentration of glucose or insulin were noted. LPS also produced an early elevation in tumor necrosis factor and a later increase in interleukin-6. These data indicate that the acute changes in the GH-IGF axis in humans in response to LPS are comparable with those observed in humans in other traumatic conditions and in animal models of endotoxemia and infection.

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