Insulin-Like Growth Factor I (IGF-I)-Binding Protein Complex Is a Better Mitogen than Free IGF-I*

Blum, Werner; Jenne, Enno W.; Reppin, F.; Kietzmann, K.; Ranke, Michael B.; Bierich, J. R.

doi:10.1210/endo-125-2-766

Cited by 313 publications

(100 citation statements)

References 35 publications

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“…Recent evidence, however, suggests that the biologic action of IGF-I is strongly modified by the relative concentrations of its binding proteins in plasma, amniotic fluid, and a variety of tissues (27)(28)(29)(30)(31)(32). Thus, a measurement in blood or tissue of the IGF-I concentration after removal of the binding proteins gives only one index of the biologic action of this growth factor.…”

Section: Resultsmentioning

confidence: 99%

Insulin-Like Growth Factor I in Substrate-Deprived, Growth-Retarded Fetal Rats

1991

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ABSTRACF. Plasma, amniotic fluid, and tissue concentra-Control animals were allowed free access to both food and water. tions of IGF-I were examined in nutritionally deprived, Sampling was performed on d 2 1 in all animals, after intraperigrowth-retarded fetal rats to determine whether IGF-I toneal pentobarbital (45 mg/kg) administration. Midline lapaconcentration serves as a marker for nutritional status. rotomy incision was used to expose the uterine horns. Fetuses in Growth retardation was induced by 72 h of maternal fast-each horn were counted, and the two inferior fetuses of each ing. Twenty-three control and 17 growth-retarded fetuses horn were sampled to match the control and test group with were individually analyzed and compared. Plasma IGF-I regard to intrauterine location. A maximum of four fetuses per concentrations were significantly lower in test compared dam were analyzed to insure matching of uterine location bewith control animals (test 56.8 f 14.9, control 87.4 f 17.5 tween groups and to minimize any metabolic impact of the ng/mL, p < 0.01). Amniotic fluid IGF-I concentrations surgical procedure. Only those fetuses in whom results from all were not different (test 14.0 f 8.7, control 12.2 f 2.6 ng/ specimens were available were included in the analyses. The mL). IGF-I concentrations obtained from both placental sampling sequence was initiated by the removal of amniotic fluid and hepatic tissues were lower in test compared with with a 19-or 20-gauge 1-mL syringe. The fetus was then removed control animals [placenta: test 293 f 25 versus control 655 from its location in the uterine horn, and an axillary cutdown f 114 ng/g (p < 0.001); hepatic: test 173 k 38 versus was performed (15). Fetal blood was collected by heparinized control 230 f 51 ng/g ( p < 0.01)]. Reductions in fetal, capillary tube, placed on ice, and centrifuged for 15 min at 12 placental, and hepatic weights in test animals were more 000 X g. The fetus was separated from the placenta, and the closely related to changes in placental IGF-I concentration fetus, placenta, and then fetal liver were weighed. The placenta than to either plasma or hepatic IGF-I concentrations. We and liver were quickfrozen in liquid nitrogen. All samples were conclude that fetal plasma IGF-I is a valuable marker for stored at -80°C until analysis. After fetal sampling, a maternal intrauterine substrate deprivation and that the growth-venous plasma sample was obtained from the inferior vena cava retarded rat fetus is accurately identified and specifically just below the renal vein. Euthanasia was performed by means characterized by a low placental concentration of extract-of exsanguination after all samples had been obtained. Individual Analyses. IGF-I concentrations in maternal and fetal plasma and amniotic fluid were determined by RIA [National Institute Circulating concentrations of IGF-I are influenced by both of Diabetes and Digestive and Kidney Diseases somatomedin-C growth hormone and nutritional status (1-10). Although the antiserum (polyclonal) cod...

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Section: Resultsmentioning

confidence: 99%

Insulin-Like Growth Factor I in Substrate-Deprived, Growth-Retarded Fetal Rats

1991

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“…IGFBPs are known to exert complex effects on the biological effects of IGFs. Whereas IGFBP-3 has been shown to either potentiate (41,42) or inhibit (43) IGF-mediated effects on osteoblasts, IGFBP-4 has consistently antagonized the IGF stimulatory effects (44,45). IGFBP-2 has been shown to potentiate (46) or antagonize the IGF-mediated effects (47,48) and its role in osteoblast biology is not known.…”

Section: Discussionmentioning

confidence: 99%

1,25-Dihydroxyvitamin D3 stimulates the production of insulin-like growth factor-binding proteins-2, -3 and -4 in human bone marrow stromal cells

Kveiborg¹,

Flyvbjerg²,

Eriksen³

et al. 2001

European Journal of Endocrinology

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Background: 1,25-Dihydroxyvitamin D 3 (calcitriol) inhibits proliferation and stimulates differentiation of multiple cell types, including osteoblasts. Human (h) bone marrow stromal cells (MSCs) are a homogenous non-hematopoietic population of cells present in the bone marrow and exhibit a less differentiated osteoblastic phenotype. The IGF system, including IGFs-I, and -II and IGF binding proteins (IGFBPs), plays an important role in osteoblast cell proliferation and differentiation. Objective: To examine the pattern of expression of the IGF system in hMSCss and its regulation by calcitriol. Methods and results: hMSCs express mRNA of both IGFs-I, and -II and IGFBPs-1 to -6 as shown by RT-PCR and northern blot analysis. As assessed by western ligand blotting (WLB) and western immmunoblot analysis, hMSCs secrete 38±42 kDa IGFBP-3, 24±28 kDa IGFBP-4 and a 33 kDa IGFBP-2. Calcitriol (dose range 10 210 ±10 27 mol/l) exerted no consistent dose-dependent effects on either IGF-I or IGF-II mRNA levels. In contrast, calcitriol treatment increased steady-state mRNA levels of IGFBPs-2, -3 and -4, but had no effect on IGFBP-5 or -6. Similarly, calcitriol increased the secretion of IGFBPs-2, -3 and -4 as determined by WLB. We found no detectable basal IGFBP-3 or IGFBP-4 protease activities in the absence or presence of calcitriol treatment.Conclusions: Our results demonstrate that hMSCs expressed a distinct pattern of IGFs and IGFBPs that may be related to their stage of differentiation. The observed increase in production of IGFBPs-2, -3 and -4 by hMSCs upon treatment with calcitriol may be an important mechanism mediating the effects of calcitriol on MSC proliferation and differentiation.

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“…Of these, IGFBP-3 is the major binding protein (23). It has been observed to potentiate the effects of IGF-I in bone (24)(25)(26). In addition, recent data clearly indicate that IGFBP-3 prolongs the half-life of circulating IGF-I levels and changes the clearance pattern of plasma IGF-I (27).…”

Section: Discussionmentioning

confidence: 99%

GH response to provocation and circulating IGF-I and IGF-binding protein-3 concentrations, the IGF-I generation test and clinical response to GH therapy in children with beta-thalassaemia

Soliman

Banna

Ansari

1998

European Journal of Endocrinology

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The causes of growth retardation of children with thalassaemia major are multifactorial. We studied the GH response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, IGF-I, IGF-binding protein-3 (IGFBP-3) and ferritin, and evaluated IGF-I generation after a single dose of GH (0.1 mg/kg per dose) in 15 prepubertal patients with thalassaemia, 15 age-matched children with constitutional short stature (CSS) (height standard deviation score less than ¹2, with normal GH response to provocation) and 11 children with isolated GH deficiency (GHD). Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (6:2 Ϯ 2:3 and 6:8 Ϯ 2:1 mg/l respectively) than the CSS group (18:6 Ϯ 2:7 and 16:7 Ϯ 3:7 mg/l respectively). They had significantly decreased circulating concentrations of IGF-I and IGFBP-3 (47:5 Ϯ 19 ng/ml and 1:2 Ϯ 0:27 mg/l respectively) compared with those with CSS (153 Ϯ 42 ng/ ml and 2:06 Ϯ 0:37 mg/l respectively), but the IGF-I and IGFBP-3 concentrations were not different from those with GHD (56 Ϯ 25 ng/ml and 1:1 Ϯ 0:32 mg/l respectively). These data demonstrate that the GH-IGF-I-IGFBP-3 axis in thalassaemic children is defective. Serum ferritin concentration correlated significantly with GH peak response to provocation (r ¼ ¹0:36, P < 0:05) and circulating IGF-I (r ¼ ¹0:47, P < 0:01) and IGFBP-3 (r ¼ ¹0:42, P < 0:01) concentrations. In the IGF-I generation test, after GH injection, the thalassaemic children had significantly lower IGF-I and IGFBP-3 levels 86:7 Ϯ 11:2 ng/ml and 2:05 Ϯ 0:51 mg/l respectively) than those in the CSS group (226 Ϯ 45:4 ng/ ml and 2:8 Ϯ 0:43 mg/l respectively). The IGF-I response was significantly higher in children with GHD (158 Ϯ 50 ng/ml) than in thalassaemic children. Six short (height standard deviation score less than ¹2) thalassaemic children who had defective GH response to provocation (<10 mg/l), all the children with GHD and eight short normal children (CSS) were treated for 1 year with human GH (18 units/m 2 per week divided into daily s.c. doses). After 1 year of GH therapy there was a marked acceleration of growth velocity in both thalassaemic children (from 3:8 Ϯ 0:6 cm/year to 7:2 Ϯ 0:8 cm/year) and controls. However, the linear acceleration of growth velocity on GH therapy was significantly slower in thalassaemic children (3:3 Ϯ 0:3 cm/year increment) compared with those with CSS (5:3 Ϯ 0:4 cm/year increment) and GHD (6:9 Ϯ 1:2 cm/year increment) (P < 0:05). Their circulating IGF-I concentration (105 Ϯ 36 ng/ml) was significantly lower than those for CSS (246 Ϯ 58 ng/ml) and GHD (189 Ϯ 52 ng/ml) after 1 year of GH therapy. These data prove that some children with b-thalassaemia major have a defective GH-IGF-I-IGFBP-3 axis and suggest the presence of partial resistance to GH.

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Insulin-Like Growth Factor I (IGF-I)-Binding Protein Complex Is a Better Mitogen than Free IGF-I*

Cited by 313 publications

References 35 publications

Insulin-Like Growth Factor I in Substrate-Deprived, Growth-Retarded Fetal Rats

Insulin-Like Growth Factor I in Substrate-Deprived, Growth-Retarded Fetal Rats

1,25-Dihydroxyvitamin D3 stimulates the production of insulin-like growth factor-binding proteins-2, -3 and -4 in human bone marrow stromal cells

GH response to provocation and circulating IGF-I and IGF-binding protein-3 concentrations, the IGF-I generation test and clinical response to GH therapy in children with beta-thalassaemia

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