Developmental changes in growth hormone, insulin-like growth factors (IGF-I and IGF-II) and IGF-binding proteins in plasma of young growing pigs

1991 ◽  
Vol 128 (3) ◽  
pp. 439-447 ◽  
Author(s):  
P. C. Owens ◽  
M. A. Conlon ◽  
R. G. Campbell ◽  
R. J. Johnson ◽  
R. King ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Total Concentration ◽  
Plasma Concentrations ◽  
Growing Pigs ◽  
Strong Positive Correlation ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Close Relationship ◽  
Igf Binding ◽  
Plasma Gh

ABSTRACT The relationship between plasma concentrations of normally secreted GH and insulin-like growth factor-I (IGF-I) was investigated in pigs after weaning. Frequent blood sampling for between 12 and 24 h showed that plasma GH was pulsatile in pigs of 10, 20 and 35 kg liveweight. Pulses were brief in duration, low in amplitude and variable in frequency. Basal and average daily plasma concentrations of GH changed significantly with development, increasing by about 50% between 10 and 20 kg liveweight. Concentrations of IGF-I in plasma showed little or no evidence of diurnal periodicity and were not increased by GH pulses. Average daily concentrations of both IGF-I and IGF-II in plasma progressively increased between 10 and 35 kg liveweight, as did the total desaturated IGF-binding protein (IGFBP) activity of plasma. A strong positive correlation was observed between the total concentration of IGFs (IGF-I plus IGF-II) in the circulation and plasma IGFBP activity. The developmental rise in IGFBP activity of plasma was associated with increased labelling with 125I-labelled human IGF-II in ligand blots of binding proteins of apparent molecular masses > 200, 50, 43 and 29 kDa. One class of binding proteins of 34·5 kDa decreased with development. This study of young growing pigs shows that normally secreted endogenous GH exerts no significant immediate control over plasma IGF-I concentrations, and that plasma levels of IGF-I and IGF-II increase with maturation in this species. The close relationship between the concentrations of IGFs and IGFBPs in plasma is consistent with recent evidence indicating that binding proteins partially regulate the levels of IGF-I and IGF-II in blood by controlling their rates of clearance from the circulation. Journal of Endocrinology (1991) 128, 439–447

Differential effects of GH stimulation on fasting and prandial metabolism and plasma IGFs and IGF-binding proteins in lean and obese sheep

1997 ◽  
Vol 154 (2) ◽  
pp. 329-346 ◽  
Author(s):  
J P McCann ◽  
S C Loo ◽  
D L Aalseth ◽  
T Abribat
Keyword(s):  
Binding Proteins ◽  
Binding Capacity ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Daily Injection ◽  
Gh Treatment ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Igf Binding ◽  
Igfbp 3

Abstract The effect of body condition per se on plasma IGFs and IGF-binding proteins (IGFBPs) and the whole-body metabolic responses to recombinant DNA-derived bovine GH (rbGH) in both the fed and the fasted state were determined in lean and dietary obese sheep (n=6/group). Sheep at zero-energy balance and equilibrium body weight were injected s.c. for 12 days with 100 μg/kg rbGH immediately before their morning feeding. Before GH treatment, fasting plasma concentrations of insulin (17·0 ± 1·9 vs 7·5 ± 0·7 μU/ml), IGF-I (345 ± 25 vs 248 ± 10 ng/ml), glucose (52·6 ± 1·1 vs 48·3 ± 0·7 mg/dl), and free fatty acid (FFA) (355 ± 45 vs 229 ± 24 nmol/ml) were greater (P<0·05) and those of GH (1·1 ± 0·2 vs 2·6 ± 0·3 ng/ml) were lower (P<0·05) in obese than in lean sheep. Fasting concentrations of IGF-II and glucagon were not affected (P>0·05) by obesity. GH concentrations were increased equivalently by 6–9 ng/ml in lean and obese sheep during GH treatment. GH caused an immediate and a marked fivefold increase in the fasting insulin level in obese sheep but only minimally affected insulin concentration in lean sheep. The increment in fasting glucose during GH treatment was greater (P<0·05) in obese (8–12 mg/dl) than in lean (2–5 mg/dl) sheep. Frequent measurements in the first 8 h after feeding and injection of excipient (day 0) or the first (day 1), sixth (day 6) and twelfth (day 12) daily injection of GH showed that prandial metabolism in both groups of sheep was affected minimally by GH. However, GH treatment on day 1 (not days 6 or 12) acutely attenuated the feeding-induced suppression of plasma FFA in both groups of sheep and this effect was significantly greater in obese than in lean sheep. Although obese sheep were hyposomatotropic, the basal and GH-induced increases in plasma IGF-I concentrations were greater (P<0·05) in obese than in lean sheep. Plasma IGF-II was unaffected by obesity and was not increased by GH stimulation. Western ligand blotting showed that IGFBP-3 accounted for approximately 50–60% of the plasma IGF-I binding capacity in sheep respectively both before and during GH treatment. Basal plasma levels of IGFBP-2 were lower (P<0·05) and those of IGFBP-3 greater (P<0·05) in obese compared with lean sheep. GH increased the level of IGFBP-3 equally in lean and obese sheep, but suppressed the expression of IGFBP-2 more (P<0·05) in lean than in obese sheep. We concluded that the diabetogenic-like actions of GH in sheep were exaggerated markedly by obesity, and were expressed more during the fasted than the fed states. The effects of GH stimulation on the endocrine pancreas may be selective for β-cells and preferentially enhanced by obesity. GH regulation of IGF-I and the IGFBPs differs in lean and obese sheep. Journal of Endocrinology (1997) 154, 329–346

Postprandial changes in plasma growth hormone, insulin, insulin-like growth factor (IGF)-I, and IGF-binding proteins in coho salmon fasted for varying periods

2009 ◽  
Vol 297 (2) ◽  
pp. R352-R361 ◽  
Author(s):  
Munetaka Shimizu ◽  
Kathleen A. Cooper ◽  
Walton W. Dickhoff ◽  
Brian R. Beckman
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Food Intake ◽  
Binding Proteins ◽  
Coho Salmon ◽  
Fasting Period ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Igf Binding ◽  
Single Meal

We examined postprandial changes in circulating growth hormone (GH), insulin, insulin-like growth factor (IGF)-I, and IGF-binding proteins (IGFBPs) in yearling coho salmon under different feeding regimes. Fish were initially fasted for 1 day, 1 wk, or 3 wk. Fasted fish were then fed, and blood was collected at 4-h intervals over 26 h. After the various periods of fasting, basal levels of insulin were relatively constant, whereas those of IGF-I, IGFBPs and GH changed in proportion to the duration of the fast. A single meal caused a rapid, large increase in the circulating insulin levels, but the degree of the increase was influenced by the fasting period. IGF-I showed a moderate increase 2 h after the meal but only in the regularly fed fish. Plasma levels of 41-kDa IGFBP were increased in all groups within 6 h after the single meal. The fasting period did not influence the response of 41-kDa IGFBP to the meal. IGFBP-1 and GH decreased after the meal to the same extent among groups regardless of the fasting period. The present study shows that insulin and IGF-I respond differently to long (weeks)- and short (hours)-term nutritional changes in salmon; insulin maintains its basal level but changes acutely in response to food intake, whereas IGF-I adjusts its basal levels to the long-term nutritional status and is less responsive to acute nutritional input. IGFBPs maintain their sensitivity to food intake, even after prolonged fasting, suggesting their critical role in the nutritional regulation of salmon growth.

scholarly journals GH/IGF e neoplasia: o que há de novo nesta associação

2005 ◽  
Vol 49 (5) ◽  
pp. 833-842 ◽  
Author(s):  
Angela M. Spinola e Castro ◽  
Gil Guerra-Júnior
Keyword(s):  
Growth Factors ◽  
Binding Proteins ◽  
De Novo ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Ciclo Celular ◽  
Igf Binding ◽  
Insulin Like Growth Factors

Estudos in vitro e em animais sugerem que os membros do sistema insulin-like growth factors (IGFs), incluindo IGF-I, IGF-II, receptores de IGF-I e IGF-II (IGF-IR e IGF-IIR), e as IGF-binding proteins (IGFBPs) podem ter um importante envolvimento no desenvolvimento e na progressão de neoplasias. Mais especificamente, as IGFs promovem a progressão do ciclo celular e inibem a apoptose tanto por ação direta com outros fatores de crescimento como por ação indireta interagindo com outros sistemas moleculares intracelulares envolvidos na promoção e/ou progressão do câncer. Além disso, inúmeros estudos epidemiológicos têm sugerido que concentrações elevadas das IGFs, independente das alterações nas IGFBPs, podem estar associadas a um aumento no risco de desenvolver determinadas neoplasias. Esta revisão tem como objetivo apresentar o envolvimento do sistema IGF na regulação tumoral, os principais estudos epidemiológicos realizados e o risco de desenvolvimento de neoplasia em pacientes (com ou sem história pessoal de neoplasia prévia) que receberam hormônio de crescimento (rhGH). É importante salientar que o uso clínico de rhGH, nas indicações aprovadas internacionalmente, é seguro e não existem evidências, até o momento, da associação com o desenvolvimento de neoplasias.

scholarly journals Insulin-like growth factor (IGF)-II binding to IGF-binding proteins and IGF receptors is modified by deletion of the N-terminal hexapeptide or substitution of arginine for glutamate-6 in IGF-II

1993 ◽  
Vol 293 (3) ◽  
pp. 713-719 ◽  
Author(s):  
G L Francis ◽  
S E Aplin ◽  
S J Milner ◽  
K A McNeil ◽  
F J Ballard ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Biological Activities ◽  
Biological Properties ◽  
Hepatoma Cells ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Anabolic Response ◽  
Igf I ◽  
Igf Binding

Recombinant insulin-like growth factor-II (IGF-II) and two structural analogues, des(1-6)IGF-II and [Arg6]-IGF-II, were produced to investigate the role of N-terminal residues in binding to IGF-binding proteins (IGFBPs) and hence the biological properties of the modified peptides. The growth factors were modelled on two previously characterized variants of IGF-I, des(1-3)IGF-I and [Arg3]-IGF-I, which both show substantially decreased binding to IGFBPs and were expressed as fusion proteins in Escherichia coli. The biological activities of the corresponding analogues of IGF-I and IGF-II were compared in rat L6 myoblasts and H35B hepatoma cells. In the L6-myoblast protein-synthesis assay, the IGF-II analogues, des(1-6)IGF-II and [Arg6]-IGF-II, were slightly more potent than IGF-II but about 10-fold less potent than IGF-I and 100-fold less potent than the respective IGF-I analogues, des(1-3)IGF-I and [Arg3]IGF-I. In H35 hepatoma cells the anabolic response measured was the inhibition of protein breakdown, and the potency order was insulin >>> [Arg3]-IGF-I > des(1-3)IGF-I > [Arg6]-IGF-II > des(1-6)IGF-II > IGF-I > IGF-II. Binding of the IGFs and their analogues to the type 1 IGF receptor in L6 myoblasts and to the insulin receptor in H35 hepatoma cells did not fully explain the observed anabolic potency differences. Moreover, binding of all four analogues to the IGFBPs secreted by L6 myoblasts and H35B hepatoma cells was greatly decreased compared with the parent IGF. We conclude that the observed anabolic response to each IGF was determined by their relative binding to the competing cell receptor and IGFBP binding sites present.

Circulating insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs) and tissue mRNA levels of IGFBP-2 and IGFBP-4 in the ovine fetus

1995 ◽  
Vol 145 (3) ◽  
pp. 545-557 ◽  
Author(s):  
J M Carr ◽  
J A Owens ◽  
P A Grant ◽  
P E Walton ◽  
P C Owens ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Mrna Level ◽  
Common Factor ◽  
Late Gestation ◽  
Mrna Levels ◽  
Igf Binding Proteins ◽  
Fetal Sheep ◽  
Igf I ◽  
Igf Binding ◽  
Igfbp 3

Abstract The IGF-binding proteins (IGFBPs) are a family of at least six structurally related proteins, which bind the IGFs and modulate their actions, including the regulation of preand postnatal growth. In this study we have examined the relationship between circulating and tissue mRNA levels of IGFBPs and related this to circulating IGFs in the fetal sheep over the gestational period when rapid growth and development occurs. Circulating IGFBP-2, as measured by Western ligand blot (WLB), increases between early and mid gestation, remains high, then declines throughout late gestation (P=0·0002). Circulating IGFBP-3 increases throughout gestation, as measured by WLB or RIA (P=0·04 and P=0·0001 respectively), as does circulating IGFBP-4 (P=0·004). These ontogenic changes in circulating IGFBPs-2 and -4 are paralleled by changes in liver mRNA for these proteins and, for IGFBP-2, by those in kidney IGFBP-2 mRNA also. This suggests that liver and kidney may be the primary contributors to circulating IGFBP-2 and the liver to circulating IGFBP-4. IGFBP-2 mRNA is present in the heart and lung in early gestation but barely detectable in these tissues after approximately 60 days gestation. IGFBP-4 mRNA is also present in the heart in early but not late gestation, but is abundant in the lung throughout gestation. These results demonstrate tissue specific and developmental regulation of IGFBPs-2 and -4 at the mRNA level. To assess any role the circulating IGFs may play in mediating these changes in IGFBPs, or vice versa, both plasma IGF-I and IGF-II were measured by RIA. Circulating IGF-I increases as gestation progresses (P=0·0001), while circulating IGF-II increases between early and mid gestation, remains high (P=0·01), then declines. Circulating IGF-I is positively correlated with fetal weight (r=0·66, P=0·03), circulating IGFBP-3 (r=0·54, P=0·01) and IGFBP-4 (r=0·52, P=0·01). Circulating IGF-II positively correlates with circulating IGFBP-2 (r=0·48, P=0·02) throughout gestation and at 1 day postnatally. These relationships are consistent with circulating IGF-I influencing IGFBPs-3 and -4, and similarly, IGF-II determining IGFBP-2, or vice versa. Alternatively, these correlations may reflect coordinate regulation of IGF and IGFBP by a common factor. Journal of Endocrinology (1995) 145, 545–557

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