Fetal plasma insulin-like growth factor-binding protein-3 concentrations are elevated following bilateral nephrectomy in fetal sheep

1995 ◽  
Vol 7 (3) ◽  
pp. 345
Author(s):  
C Beanland ◽  
C Browne ◽  
R Young ◽  
J Owens ◽  
P Walton ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Bilateral Nephrectomy ◽  
Fetal Sheep ◽  
Factor Binding ◽  
Fetal Plasma ◽  
Igf I ◽  
Igf Binding ◽  
Igfbp 3

Insulin-like growth factors mediate many of the effects of growth hormone and are important in the regulation of growth, especially in the fetus where growth is less dependent on circulating growth hormone. In the ovine fetus, insulin-like growth factor-I (IGF-I) is bound mainly to the low molecular weight insulin-like growth factor-binding proteins (IGFBP), IGFBP-1 and IGFBP-2, with little binding to IGFBP-3 until near term at 147 days gestation. To determine if there was any difference in plasma IGF-I and IGFBP-3 concentrations in growth-retarded fetal sheep with altered renal status, concentrations were measured by specific radioimmunoassay from bilaterally nephrectomized fetal sheep between Days 113 and 135 gestation. Plasma IGFBP-3 concentrations were significantly (P < 0.001) increased in bilaterally nephrectomized fetuses (4.19 +/- 0.19 micrograms mL-1, n = 7) compared with control fetuses (2.33 +/- 0.10 micrograms mL-1, n = 7). There was no change in plasma IGFBP-3 concentration with gestational age in either experimental group. Maternal plasma IGFBP-3 concentrations did not differ between the bilateral nephrectomy group (3.11 +/- 0.09 micrograms mL-1, n = 7) and the control group (3.25 +/- 0.11 micrograms mL-1, n = 7) and showed no change within groups over the experimental period. Total plasma IGF-I concentrations in bilaterally nephrectomized fetuses and ewes were similar to those in control fetuses and ewes. The results indicate that the profile of IGF binding in fetal plasma is altered in the anephric fetal sheep. In nephrectomized fetal sheep, increased IGFBP-3 concentrations, and therefore increased IGF-binding capacity in fetal plasma, may have contributed to a decrease in free IGF in plasma and decreased IGF-I bioactivity. This would provide a possible mechanism for the growth retardation reported in bilaterally nephrectomized fetal sheep.

Long-term treatment of Laron type dwarfs with insulin-like growth factor-1 increases serum insulin-like growth factor-binding protein-3 in the absence of growth hormone activity

1993 ◽  
Vol 128 (2) ◽  
pp. 144-149 ◽  
Author(s):  
Hannah Kanety ◽  
Avraham Karasik ◽  
Beatrice Klinger ◽  
Aviva Silbergeld ◽  
Zvi Laron
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Binding Protein ◽  
Serum Insulin ◽  
Continuous Treatment ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Long Term Treatment ◽  
Igf I ◽  
Igfbp 3

Insulin-like growth factor binding protein-3 (IGFBP-3) is the major carrier of insulin-like growth factor I (IGF-1) in serum, and its production is growth hormone (GH) dependent. It is unclear whether in humans IGFBP-3 production is directly regulated by GH or mediated via IGF-I. We addressed this question in six patients with Laron-type dwarfism, a syndrome characterized by the absence of GH receptor activity (LTD), who were chronically treated with recombinant IGF-I. Analysis of the electrophoretic profiles of serum IGFBPs in these patients by Western ligand blotting revealed an extremely low IGFBP-3 level. A striking progressive increase in serum IGFBP-3 was observed with continuous treatment, despite the absence of GH action. In LTD children, serum IGFBP-3 increased up to 19-fold after six months of therapy and equalled levels observed in controls, whereas in adult LTD patients the increase was smaller. A rise in serum levels of 34, 30 and 24 kDa BPs (presumably IGFBP-2, -1 and -4, respectively was also noted with chronic IGF-I therapy. This proof of GH-independent induction of IGFBP-3 by IGF-1 may be a major advantage in the therapeutic use of biosynthetic IGF-I in several types of short stature children.

scholarly journals Ligand-binding characteristics of recombinant amino- and carboxyl-terminal fragments of human insulin-like growth factor-binding protein-3

2001 ◽  
Vol 169 (1) ◽  
pp. 123-133 ◽  
Author(s):  
M Galanis ◽  
SM Firth ◽  
J Bond ◽  
A Nathanielsz ◽  
AA Kortt ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Igf I ◽  
Igf Binding ◽  
Carboxyl Terminal ◽  
Igfbp 3

Insulin-like growth factor-binding protein-3 (IGFBP-3) is a member of a family of structurally conserved proteins (IGFBP-1 to -6) which act as carriers and regulators of the mitogenic peptide hormones IGF-I and IGF-II. Members of the IGFBP family share conserved cysteine-rich amino- and carboxyl-terminal regions. The amino-terminal domain of these proteins is recognised to contain an IGF-binding determinant, but evidence to support a binding site in the carboxyl-terminal region of the protein is less rigorous. To further investigate this, we have synthesised both the amino-terminal (residues 1-88; N-88) and carboxyl-terminal (residues 165-264; C-165) domains of human IGFBP-3 in bacteria, as fusion proteins with a carboxyl-terminal FLAG peptide. Although only C-165 showed binding to IGF-I and -II by solution-binding assays, both N-88 and C-165 demonstrated binding to IGF-I and -II by biosensor analysis albeit with reduced affinities compared with full-length IGFBP-3. Only the carboxyl-terminal fragment (C-165) was able to form hetero-trimeric complexes with IGF-I and the acid-labile subunit (ALS). We conclude that the carboxyl-terminal domain of IGFBP-3 contains an IGF-binding determinant and can form ternary complexes with ALS.

No evidence for reduced spontaneous or growth-hormone-stimulated serum levels of insulin-like growth factor (IGF)-I, IGF-II or IGF binding protein 3 in women with spinal osteoporosis

1994 ◽  
Vol 131 (2) ◽  
pp. 150-155 ◽  
Author(s):  
M Kassem ◽  
K Brixen ◽  
W Blum ◽  
L Mosekilde ◽  
EF Eriksen
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Binding Protein ◽  
Serum Levels ◽  
Insulin Like Growth Factor ◽  
Spinal Osteoporosis ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

Kassem M, Brixen K, Blum W, Mosekilde L, Eriksen EF. No evidence for reduced spontaneous or growth-hormone-stimulated serum levels of insulin-like growth factor (IGF)-I, IGF-II or IGF binding protein 3 in women with spinal osteoporosis. Eur J Endocrinol 1994;131:150–5. ISSN 0804–4643 To test the hypothesis that a dysfunctional growth hormone (GH)–insulin-like growth factor (IGF) axis may play a role in the pathogenesis of osteoporosis, we compared the levels of IGF-I, IGF-II and IGF binding protein 3 (IGFBP-3) in 15 women with spinal osteoporosis (i.e. at least one non-traumatic vertebral fracture) and 15 normal age-matched women. Furthermore, the response to 3 days' treatment with recombinant human GH (r-hGH) (0.2 IU kg−1·day−1) was determined. The basal levels of IGF-I, IGF-II and IGFBP-3 were similar in patients and controls (mean ± sem): IGF-I, 16.5 ± 1.3 versus 16.0 ± 1.3 nmol/l (NS); IGF-II, 79.9 ± 3.6 versus 72.5 ± 4.1 nmol/l (NS); and IGFBP-3, 125.7 ± 6.5 versus 130.3 ± 7.8 nmol/l (NS). Stimulation with r-hGH elicited increased levels of IGF-I, IGF-II and IGFBP-3 within both groups (p < 0.001). The maximal values expressed as a percentage of baseline were: IGF-I, 341 ± 26% versus 369 ± 22%, IGF-II, 125 ± 4% versus 119 ± 5%, IGFBP-3, 141 ± 5% versus 147 ± 7% in osteoporotic patients and controls, respectively. No significant differences were observed between patients and controls in either their maximal response or in the area under the response curves. Our results do not support the hypothesis of a dysfunctional GH–IGF axis in women with spinal osteoporosis. Kim Brixen, University Department of Endocrinology and Metabolism, Aarhus Amtssygehus, Tage-Hansens gade 2, DK-8000 Aarhus C, Denmark

Clinical utility of insulin-like growth factor binding protein-3 in the evaluation and treatment of short children with suspected growth hormone deficiency

1994 ◽  
Vol 131 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Yukihiro Hasegawa ◽  
Tomonobu Hasegawa ◽  
Taiji Aso ◽  
Shinobu Kotoh ◽  
Osamu Nose ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Hormone Deficiency ◽  
Insulin Like Growth Factor ◽  
Normal Children ◽  
Gh Treatment ◽  
Factor Binding ◽  
Short Children ◽  
Igf I ◽  
Igfbp 3

Hasegawa Y, Hasegawa T, Aso T, Kotoh S, Nose 0, Ohyama Y, Araki K, Tanaka T, Saisyo S, Yokoya S, Nishi Y, Miyamoto S, Sasaki N, Kurimoto F, Stene M, Tsuchiya Y, Clinical utility of insulin-like growth factor binding protein-3 in the evaluation and treatment of short children with suspected growth hormone deficiency. Eur J Endocrinol 1994;131:27–32. ISSN 0804–4643 We have shown previously that serum insulin-like growth factor binding protein-3 (IGFBP-3) levels have good predictive value for complete, but not partial, growth hormone deficiency (GHD). In this study, we compare IGFBP-3 levels in short children previously divided into groups on the basis of their post-stimulation GH levels. Complete GHD (N = 59) included those children with peak poststimulation GH < 5 μg/l. The partial GHD group (N = 49) had post-stimulation GH peaks of > 5 μg/l but < 10 μg/l. The normal children with short stature (N = 103) had post-stimulation GH peaks > 10 μg/l. Partial GHD and normal children with short stature also were divided into either low IGF-I or normal IGF-I subgroups. The clinical sensitivity of IGFBP-3 for complete GHD was 92%, whereas its sensitivity for partial GHD was 39%. For partial GHD, among those with low IGF-I (N = 19) 68% were also low for IGFBP-3, while 80% of those with normal IGF-I (N = 30) were also normal for IGFBP-3. The clinical specificity of IGFBP-3 for normal children with short stature was 69%. For these groups, among those with low IGF-I (N = 22) 73% also were low for IGFBP-3, while 80% of those with normal IGF-I (N = 81) also were normal for IGFBP-3. In addition, we tested whether IGFBP-3 can predict the response to GH treatment in prepubertal children by comparing pretreatment IGFBP-3 with the height gain achieved by 1 year of GH treatment. The incremental growth velocity during treatment correlated significantly with the pretreatment IGFBP-3 sd score (N = 46 r = –0.80, p < 0.005). The baseline IGFBP-3 sd score for all subjects correlated (N = 171, r = 0.51 p < 0.0001) with height. These data suggest that IGFBP-3 may reflect GH secretion status in most children being evaluated for GHD and that a low pretreatment IGFBP-3 sd score predicts improved growth during the first year of GH treatment. Yukihiro Hasegawa, Division of Endocrinology and Metabolism, Tokyo Metropolitan Kiyose Children's Hospital, 1-3-1 Umezono, Kiyose, Tokyo 204, Japan

scholarly journals Effect of Mild Hypoinsulinemia on Renal Hypertrophy: Growth Hormone/Insulin-Like Growth Factor I System in Mild Streptozotocin Diabetes

2002 ◽  
Vol 3 (4) ◽  
pp. 257-264 ◽  
Author(s):  
Mogher Khamaisi ◽  
Allan Flyvbjerg ◽  
Ziv Haramati ◽  
Gadi Raz ◽  
Isaiah D. Wexler ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Experimental Diabetes ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

The metabolic aberrations associated with diabetes mellitus profoundly alter the growth hormone/insulin-like growth factor I (GH/IGF-I) system. In severe experimental diabetes, serum IGF-I level is reduced, reflecting altered hepatic expression. On the other hand, increased levels of kidney IGF-I have been implicated in the development of diabetic kidney disease. This study aimed to examine the effect of mild experimental diabetes with hypoinsulinemia on both the systemic and renal GH/IGF-I systems in a low-dose streptozotocin (STZ)-induced diabetic rat. Diabetic animals with mild hypoinsulinemia developed renal hyperfiltration within 3 days of diabetes, whereas the renal size increased significantly only between 30 and 48 days of diabetes. Plasma GHlevels were unchanged during the entire course of the study, but a decrease in serum IGF-I, IGF-binding protein 3 (IGFBP-3), and IGF-binding protein 4 (IGFBP-4) occurred after 10, 30, and 48 days. Kidney IGF-I and IGF-binding protein 1 (IGFBP-1) mRNA expression increased after 10 and 30 days of diabetes. A significant increase in kidney IGFBP-1/2, IGFBP-3, and IGFBP-4 proteins was seen after 48 days of diabetes.Apositive correlations was found between renal growth and insulin/glucose ratio (r= .57), kidney IGF-I (r= .57), IGFBP-1 mRNA(r= .43), IGFBP-1/2 (r= .41), and IGFBP-4 levels (r= .40). These results demonstrate hyperfiltration within 3 days of diabetes and a similar response in the IGF-I system in mildly and severely hypoinsulinemic rats; however, renomegaly develops slower in mildly diabetic rats at least partly due to delayed changes in the renal IGF and IGF BPs.

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