scholarly journals Partial Primary Deficiency of Insulin-Like Growth Factor (IGF)-I Activity Associated with IGF1 Mutation Demonstrates Its Critical Role in Growth and Brain Development

2009 ◽  
Vol 23 (11) ◽  
pp. 1936-1936
Author(s):  
Irène Netchine ◽  
Salah Azzi ◽  
Muriel Houang ◽  
Danielle Seurin ◽  
Laurence Perin ◽  
...  
Keyword(s):  
Brain Development ◽  
Critical Role ◽  
Growth Failure ◽  
Normal Growth ◽  
Serum Levels ◽  
Partial Loss ◽  
Therapeutic Implications ◽  
Molecular Defects ◽  
Igf I ◽  
Igfbp 3

ABSTRACT Context IGF-I is essential for fetal and postnatal development. Only three IGF1 defects leading to dramatic loss of binding to its type 1 receptor, IGF-1R, have been reported. Patient We describe a very lean boy who has intrauterine growth restriction and progressive postnatal growth failure associated with normal hearing, microcephaly, and mild intellectual impairment. He had markedly reduced concentrations of IGF-I, with IGFBP-3 and ALS serum levels in the upper normal range or above. IGF-I serum concentrations differed according to the immunoassay used. A higher than average GH dose was required for catch-up growth. Given the mismatch between IGF-I and IGFBP-3 levels, we sequenced his IGF1 gene. Result We identified a homozygous missense IGF1 mutation. This causes the replacement of a highly conserved amino acid (arginine 36) by a glutamine (R36Q) in the C domain of the predicted peptide. We showed that the abnormal IGF-I peptide has reduced mitogenic activity and partial loss of binding to its receptor IGF-1R. The patient’s IGF-I level was undetectable in a highly specific monoclonal assay but elevated in a polyclonal assay. Conclusion This first report of mild deficiency of IGF-I activity demonstrates that the integrity of IGF-I signaling is important for normal growth and brain development. Molecular defects leading to partial loss of IGF-I activity may not be uncommon in patients born small for gestational age. The characterization of this complex phenotype and identification of such molecular defects have therapeutic implications, particularly now that, in addition to GH, recombinant IGF-I is available for clinical use.

scholarly journals Failure of exogenous IGF-I to restore normal growth in rats submitted to dietary zinc deprivation

1998 ◽  
Vol 159 (2) ◽  
pp. 211-217 ◽  
Author(s):  
NX Ninh ◽  
D Maiter ◽  
J Verniers ◽  
P Lause ◽  
JM Ketelslegers ◽  
...  
Keyword(s):  
Zinc Deficiency ◽  
Growth Retardation ◽  
Serum Insulin ◽  
Growth Failure ◽  
Normal Growth ◽  
Normal Diet ◽  
Dietary Zinc ◽  
Deficient Diet ◽  
Igf I ◽  
Igfbp 3

Dietary zinc deficiency in rats causes growth retardation associated with decreased circulating IGF-I concentrations. To investigate the potential role of low IGF-I in this condition, we attempted to reverse the growth failure by administration of exogenous IGF-I. Rats were fed for 4 weeks a zinc-deficient diet (ZD, Zn 0 ppm) or were pair-fed a zinc-normal diet (PF, Zn 75 ppm). We compared the anabolic action of recombinant human (rh) IGF-I infused at the dose of 120 microg/day for the last experimental week in ZD, PF and freely fed control (CTRL) rats. Zinc deficiency caused growth stunting (weight gain 47% of PF; P<0.001), decreased circulating IGF-I (52% of PF; P<0.01) and liver IGF-I mRNA (67% of PF; P<0.01). Serum insulin-like growth factor-binding protein-3 (IGFBP-3) assessed by ligand blot was also reduced in ZD rats (65% of PF; P<0. 01). While exogenous IGF-I increased body weight in CTRL (+12 g; P<0. 01) and PF (+7 g; not significant) animals, growth was not stimulated in ZD rats (-1.5 g) in comparison with the corresponding untreated groups. However, circulating IGF-I and IGFBP-3 levels were restored by IGF-I infusion to levels similar to those in untreated CTRL rats. In conclusion, restoration of normal circulating levels of IGF-I and IGFBP-3 by rhIGF-I infusion fails to reverse the growth retardation induced by zinc deficiency. These results suggest that growth retardation related to zinc deficiency is not only caused by low serum IGF-I concentrations, but also by inhibition of the anabolic actions of IGF-I.

scholarly journals Effects of Eight Months Treatment with Graded Doses of a Growth Hormone (GH)-Releasing Peptide in GH-Deficient Children1

1998 ◽  
Vol 83 (7) ◽  
pp. 2355-2360
Author(s):  
Verónica Mericq ◽  
Fernando Cassorla ◽  
Teresa Salazar ◽  
Alejandra Avila ◽  
Germán Iñiguez ◽  
...  
Keyword(s):  
Growth Failure ◽  
Serum Levels ◽  
Duration Of Action ◽  
Prepubertal Children ◽  
Routes Of Administration ◽  
Gh Secretion ◽  
Igf I ◽  
Over Time ◽  
Stimulation Of ◽  
Igfbp 3

Stimulation of pituitary GH secretion with administered GHRH can be effective therapy for those GH deficient (GHD) patients whose disorder results from insufficient endogenous GHRH secretion. We have previously shown that most such patients also respond acutely to the GH-releasing peptides (GHRP’s), which have a different mechanism of action from GHRH, with release of GH. In this study we tested whether the GH response to a newer GHRP, GHRP-2, would be sustained over time. Six prepubertal children with GHD and growth failure received stepwise increasing sc doses of GHRP-2, at 0.3, 1.0, and 3.0 μg/kg/day, in successive 2-month treatment periods, with monitoring of overnight 12 h episodic GH secretion and toxicity measures at the end of each period. During a fourth 2-month period, they received 3 μg/kg GHRP-2 together with 3 μg/kg sc GHRH. Serum levels of IGF-I and IGFBP-3 were also measured, and stadiometer height measurements were recorded. GHRP-2 administration produced a dosewise increase in overnight GH secretion. GH profiles showed that the effect of GHRP-2 injections was relatively brief, with little effect upon GH secretion later in the night. Serum levels of IGF-I and of IGFBP-3 did not increase. Growth velocity was higher during GHRP-2 treatment than during pretreatment and post-treatment evaluations. There were no side effects or toxicities observed. Thus GHRP-2 is well tolerated and is able to stimulate GH secretion. Formulations or routes of administration that allow for a longer duration of action will likely be needed to use GHRP-2 in therapy.

Serum levels of insulin-like growth factors (IGF-I and IGF-II) and their binding protein (IGFBP-3) are not elevated in pancreatic cancer

1997 ◽  
Vol 22 (2) ◽  
pp. 95-100
Author(s):  
James D. Evans ◽  
Margaret C. Eggo ◽  
Ian A. Donovan ◽  
Simon R. Bramhall ◽  
John P. Neoptolemos
Keyword(s):  
Pancreatic Cancer ◽  
Growth Factors ◽  
Binding Protein ◽  
Serum Levels ◽  
Igf I ◽  
Igfbp 3 ◽  
Insulin Like Growth Factors

scholarly journals Abnormal Sex Chromosome Constitution and Longitudinal Growth: Serum Levels of Insulin-Like Growth Factor (IGF)-I, IGF Binding Protein-3, Luteinizing Hormone, and Testosterone in 109 Males with 47,XXY, 47,XYY, or Sex-Determining Region of the Y Chromosome (SRY)-Positive 46,XX Karyotypes

2008 ◽  
Vol 93 (1) ◽  
pp. 169-176 ◽  
Author(s):  
Lise Aksglaede ◽  
Niels E. Skakkebaek ◽  
Anders Juul
Keyword(s):  
Sex Chromosome ◽  
Serum Levels ◽  
Reproductive Hormones ◽  
Chromosome Constitution ◽  
Sitting Height ◽  
Igf I ◽  
Igf Binding ◽  
Xx Males ◽  
Igf Binding Protein ◽  
Igfbp 3

Abstract Context: Growth is a highly complex process regulated by the interaction between sex steroids and the GH IGF-axis. However, other factors such as sex chromosome-related genes play independent roles. Aim: The aim of the study was to evaluate the role of abnormal chromosome constitution for longitudinal growth in relation to reproductive hormones, IGF-I, and IGF binding protein (IGFBP)-3. Setting: The study was conducted at an outpatient clinic, Copenhagen University Hospital. Participants: Participants included 86 47,XXY males, 14 46,XX-males, and nine 47,XYY. Main Outcome Measures: Standing and sitting height, serum levels of reproductive hormones, IGF-I, and IGFBP-3 were measured. Results: In boys with 47,XXY and 47,XYY karyotypes, growth was accelerated already in childhood, compared with healthy boys. 46,XX-males were significantly shorter than healthy boys but matched the stature of healthy girls. In 47,XXY sitting height to height ratios were lower than expected, whereas body proportions in 46,XX-males and 47,XYY were normal. In all subjects serum levels of IGF-I and IGFBP-3 were within normal limits. The boys with 46,XX and 47,XXY karyotypes presented with low normal testosterone and elevated LH levels after puberty, whereas the sex hormone secretion of the 47,XYY boys remained normal. Conclusion: We found accelerated growth in early childhood in boys with 47,XXY and 47,XYY karyotypes, whereas 46,XX-males were shorter than controls. These abnormal growth patterns were not reflected in circulating levels of IGF-I and IGFBP-3. The boys with 46,XX and 47,XXY karyotypes developed hypogonadism in puberty, but androgen secretion in 47,XYY boys remained normal. The abnormal stature of these patients may be a result of abnormal gene expression due to the underlying chromosome aberration resulting in excessive expression of growth-related genes.

scholarly journals Body mass index, waist circumference and waist–hip ratio and serum levels of IGF-I and IGFBP-3 in European women

2006 ◽  
Vol 30 (11) ◽  
pp. 1623-1631 ◽  
Author(s):  
I T Gram ◽  
T Norat ◽  
S Rinaldi ◽  
L Dossus ◽  
A Lukanova ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Waist Circumference ◽  
Body Mass ◽  
Serum Levels ◽  
Waist Hip Ratio ◽  
Igf I ◽  
European Women ◽  
Igfbp 3

scholarly journals Serum Levels of Ghrelin, Leptin, IGF-I, IGFBP-3, Insulin, Thyroid Hormones and Cortisol in Prepubertal Children with Iron Deficiency

2007 ◽  
Vol 54 (6) ◽  
pp. 985-990 ◽  
Author(s):  
Pinar ISGUVEN ◽  
Ilknur ARSLANOGLU ◽  
Melih EROL ◽  
Metin YILDIZ ◽  
Erdal ADAL ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Thyroid Hormones ◽  
Serum Levels ◽  
Prepubertal Children ◽  
Igf I ◽  
Igfbp 3

scholarly journals Insulin infusion increases levels of free IGF-I and IGFBP-3 proteolytic activity in patients after surgery

2001 ◽  
Vol 281 (4) ◽  
pp. E736-E741 ◽  
Author(s):  
J. Nygren ◽  
C. Carlsson-Skwirut ◽  
K. Brismar ◽  
A. Thorell ◽  
O. Ljungqvist ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Growth Factor ◽  
Proteolytic Activity ◽  
Insulin Infusion ◽  
Serum Levels ◽  
Insulin Resistant ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

We have studied the effects of insulin on the bioavailability of insulin-like growth factor (IGF) I in insulin-resistant patients after surgery. Serum levels of total IGF-I (tIGF-I), free IGF (fIGF)-I, fIGF-II, and IGF-binding protein (IGFBP) 1 and IGFBP-3 proteolytic activity (IGFBP-3-PA), determined on the day before surgery and on the 1st postoperative day, were related to insulin sensitivity measured by a hyperinsulinemic, normoglycemic clamp. Before surgery, the decreased tIGF-I ( P < 0.05) in response to insulin infusion was accompanied by an 18% reduction of IGFBP-1 ( P < 0.001), while IGFBP-3-PA remained unchanged. Levels of fIGF-I and fIGF-II were not changed by insulin infusions. After surgery, IGFBP-3-PA increased ( P < 0.05) during insulin infusion, and this was associated with an increase in tIGF-I ( P < 0.001) and fIGF-I ( P < 0.01), while no significant change was found in fIGF-II. The reduction in IGFBP-1 in response to insulin infusion was not affected by surgery. The change in IGFBP-3-PA during insulin infusion after surgery was related to the corresponding change in fIGF-I ( r 2 = 0.26, P < 0.05) and postoperative insulin sensitivity ( r 2 = −0.22, P < 0.05). These data suggest that increased IGFBP-3-PA during insulin infusion after surgery governs the increased levels of fIGF-I, while insulin-induced suppression of IGFBP-1 was not affected by surgery. We propose that, in catabolic, postoperative patients, increased levels of insulin from exogenous or, possibly, endogenous sources (nutritionally induced) may be a signal to increase IGF-I bioavailability by increased expression of IGFBP-3-PA to counteract further deterioration in glucose metabolism.

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