Maternal serum insulin-like growth factor (IGF-I) and binding proteins IGFBP-1 and IGFBP-3 at 11–13 weeks’ gestation in pregnancies delivering small for gestational age neonates

Measurement of insulin-like growth factor II (IGF-II) in human serum is complicated by the presence of IGF binding proteins and usually involves cumbersome extraction procedures followed by radioimmunoassay. We have utilized an extraction process developed for measuring insulin-like growth factor II in ovine serum using Sephacryl HR100, and have applied this to the extraction of human samples followed by radioimmunoassay for human IGF-II. The assay yielded 98% recovery of unlabelled IGF-II, parallelism between dilutions of eluate and the standard curve, complete removal of binding proteins and near-complete removal of IGF-I, and intra- and interassay coefficients of variation of 5% and 9%, respectively. The normal range for serum IGF-II in women was 490–1056 μg/L, and IGF-II levels were positively correlated with serum concentrations of insulin-like growth factor binding protein-3 (IGFBP-3) but not with IGF-I levels. Mean serum concentrations of IGF-II were reduced below normal in a number of hypopituitary patients and children with short stature and IGF-II concentrations in these subjects correlated positively with IGF-I and IGFBP-3. In acromegalic patients IGF-II levels were usually normal and were negatively correlated with IGF-I concentrations. From our experience with the above results the present assay appears particularly suitable for clinical measurements and research projects where high sample throughput is required.

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Physical capacity influences the response of insulin-like growth factor and its binding proteins to training

Journal of Applied Physiology ◽

10.1152/japplphysiol.00145.2002 ◽

2002 ◽

Vol 93 (5) ◽

pp. 1669-1675 ◽

Cited By ~ 62

Author(s):

Lars Rosendal ◽

Henning Langberg ◽

Allan Flyvbjerg ◽

Jan Frystyk ◽

Hans Ørskov ◽

...

Keyword(s):

Growth Factor ◽

Physical Training ◽

Binding Proteins ◽

Insulin Like Growth Factor ◽

Initial Training ◽

Serum Samples ◽

Fitness Level ◽

Igf System ◽

Igf I ◽

Igfbp 3

The influence of initial training status on the response of circulating insulin-like growth factor (IGF) and its binding proteins (IGFBP) to prolonged physical training was studied in young men. It was hypothesized that highly standardized training would result in more extensive changes in the circulating IGF system in untrained subjects because of lower fitness level. Seven untrained (UT) and 12 well-trained (WT) individuals performed 11 wk of intense physical training (2–4 h daily). Fasting serum samples were analyzed for total and free IGF-I and -II, for IGFBP-1 to -4, as well as for IGFBP-3 proteolysis. Eleven weeks of physical training resulted in decreased levels of total IGF-I, free IGF-I, and IGFBP-4 in both the UT and WT groups. In the UT group, IGFBP-2 increased, IGFBP-3 decreased [from 4,255 ± 410 (baseline) to 3,896 ± 465 (SD) μg/l ( week 4); P < 0.05], and IGFBP-3 proteolysis increased [from 28 ± 8% (baseline) to 37 ± 7% ( week 4) and 39 ± 12% ( week 11); P < 0.05], whereas no significant changes were found in the WT group. In conclusion, intense physical training results in a marked influence on the IGF system and its binding proteins with generally more extensive changes seen in the untrained individuals. Also, prolonged physical training resulted in increased IGFBP-3 proteolysis in previously untrained individuals only, indicating that intense physical training affects trained and untrained individuals differently.

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Evaluation of serum insulin-like growth factor binding proteins (IGFBP) in Angus cattle divergently selected for serum IGF-I concentration

Domestic Animal Endocrinology ◽

10.1016/j.domaniend.2003.06.002 ◽

2003 ◽

Vol 25 (4) ◽

pp. 345-358 ◽

Cited By ~ 12

Author(s):

M Pagan ◽

M.E Davis ◽

D.A Stick ◽

R.C.M Simmen ◽

N.E Raney ◽

...

Keyword(s):

Growth Factor ◽

Binding Proteins ◽

Serum Insulin ◽

Insulin Like Growth Factor ◽

Factor Binding ◽

Angus Cattle ◽

Igf I

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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

Acta Endocrinologica ◽

10.1530/acta.0.1280144 ◽

1993 ◽

Vol 128 (2) ◽

pp. 144-149 ◽

Cited By ~ 41

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.

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Age- gender- and tanner stage-specific reference intervals for serum insulin-like growth factor binding protein 3 (IGFBP-3) and the insulin-like growth factor I (IGF-I) to IGFBP-3 molar ratios in healthy school children of a north indian city

Endocrine Abstracts ◽

10.1530/endoabs.77.p92 ◽

2021 ◽

Author(s):

Teja KV Ravi ◽

RK Marwaha ◽

Bhanu Malhotra ◽

Naresh Sachdeva ◽

Liza Das ◽

...

Keyword(s):

Growth Factor ◽

Serum Insulin ◽

Tanner Stage ◽

Reference Intervals ◽

Specific Reference ◽

Insulin Like Growth Factor ◽

Molar Ratios ◽

Igf I ◽

Indian City ◽

Igfbp 3

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Comparison of the effectiveness of various procedures for reducing or eliminating insulin-like growth factor-binding protein interference with insulin-like growth factor-I radioimmunoassays on porcine sera

Journal of Endocrinology ◽

10.1677/joe.0.1400229 ◽

1994 ◽

Vol 140 (2) ◽

pp. 229-237 ◽

Cited By ~ 22

Author(s):

R S Frey ◽

M R Hathaway ◽

W R Dayton

Keyword(s):

Molecular Weight ◽

Growth Factor ◽

Binding Proteins ◽

Insulin Like Growth Factor ◽

Factor Binding ◽

Factor I ◽

Igf I ◽

Growth Factor I ◽

Igfbp 3 ◽

Glycyl Glycine

Abstract We have examined the efficacy of various methods for reducing the interference of insulin-like growth factor-binding proteins (IGFBPs) with insulin-like growth factor-I (IGF-I) radioimmunoassays (RIAs) run on porcine sera. Acid–ethanol (AE) extraction, AE extraction followed by cryoprecipitation, glycyl–glycine (GG) extraction, GG extraction followed by Sephadex G-50 chromatography in 1 mol acetic acid/l (GG/G-50), and Sep-Pak chromatography were analysed. To provide a range of IGF-I and IGFBP levels, sera obtained from control, hypophysectomized, diabetic and somatotrophin-treated pigs were used. Recoveries of IGF-I added to sera prior to treatments other than Sep-Pak chromatography ranged from 85 to 105% and were not significantly different. In contrast, Sep-Pak chromatography gave extremely variable recoveries. 125I-Labelled IGF-I ligand blotting showed that GG extraction followed by acid G-50 chromatography was by far the most effective method of removing or inactivating IGFBPs in porcine sera. Consequently, this procedure was used as a standard against which to compare other extraction procedures. GG extraction alone removed or inactivated low molecular weight binding proteins but appeared to have little effect on IGFBP-3. AE extraction reduced the level of IGFBP-3 but had little effect on lower molecular weight binding proteins. Even though none of the tested procedures completely removed or inactivated the binding proteins, all samples yielded IGF-I displacement curves that were parallel to that obtained for IGF-I standard. Despite yielding parallel displacement curves, sera extracted by various methods gave dramatically different apparent IGF-I levels when subjected to IGF-I RIA. IGF-I RIA of GG extracted sera yielded IGF-I values that were closest to those obtained for identical serum samples subjected to glycyl-glycine extraction followed by G-50 chromatography. For sera from control, hypophysectomized, diabetic and somatotrophin-treated pigs, the relationship of the IGF-I level in GG-extracted sera to that in GG-extracted, acid G-50 chromatographed (GG/G-50) sera was √GG=1·13√GG/G-50−0·23 (r2=0·98). Consequently, GG extraction can be used to remove IGFBP interference with IGF-I RIAs of porcine sera from normal, hypophysectomized, diabetic and somatotrophin-treated animals. Journal of Endocrinology (1994) 140, 229–237

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Responses of insulin-like growth factor binding protein-1 (IGFBP-1) and the IGFBP-3 complex to administration of insulin-like growth factor-I

Acta Endocrinologica ◽

10.1530/acta.0.1280101 ◽

1993 ◽

Vol 128 (2) ◽

pp. 101-108 ◽

Cited By ~ 28

Author(s):

Robert C Baxter ◽

Naomi Hizuka ◽

Kazue Takano ◽

Sara R Holman ◽

Kumiko Asakawa

Keyword(s):

Single Dose ◽

Growth Factor ◽

Food Intake ◽

Binding Proteins ◽

Insulin Like Growth Factor ◽

Factor Binding ◽

Factor I ◽

Igf I ◽

Highly Correlated ◽

Igfbp 3

The importance of insulin-like growth factor binding proteins (IGFBPs) in modulating the bioactivity of administered IGFs is poorly understood. This study examines responses of IGFBP-1 and the IGFBP-3 complex to recombinant human IGF-I. Eight fasted subjects received a single dose of 0.1-0.125 mg/kg IGF-I sc. This caused a 10-fold rise in IGFBP-1 over 6 h. falling rapidly after food intake. Peak (6-h) IGFBP-1 values were highly correlated with peak post-prandial (8-h) glucose values (r = 0.941). IGFBP--3 showed little response, decreasing slightly over the 48-h period following IGF-I. Adaptive changes in IGFBPs were studied in fed adults injected daily for 7 days with IGF-I, 0.1 mg/kg sc. Following the first injection. IGFBP-1 had a markedly blunted response compared to that in fasted subjects. However, after the seventh IGF-I injection, a 3.5-fold greater IGFBP-1 response to the same IGF-I dose was seen. Concomitantly with the increased IGFBP-1 responsiveness, mean immunoreactive IGFBP-3 and acidlabile subunit levels decreased significantly (p< 0.005), whereas IGFBP-2 detected by immunoblotting increased. Thus IGF-I administration causes changes in IGFBPs which may be important in regulating IGF-1 bioavailability.

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