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

1993 ◽  
Vol 128 (2) ◽  
pp. 101-108 ◽  
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.

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

1994 ◽  
Vol 140 (2) ◽  
pp. 229-237 ◽  
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

Insulin-like growth factor-I (IGF-I) and IGF-binding proteins both decline in the rat during late pregnancy

1990 ◽  
Vol 127 (3) ◽  
pp. 383-390 ◽  
Author(s):  
S. E. Gargosky ◽  
P. E. Walton ◽  
P. C. Owens ◽  
J. C. Wallace ◽  
F. J. Ballard
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Late Pregnancy ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Pregnant Rats ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Igfbp 3

ABSTRACT Insulin-like growth factor-I (IGF-I), IGF-II and IGF-binding proteins (IGFBP) were examined in rat serum during pregnancy and lactation. IGF-I concentrations determined after acid column chromatography of serum were low during the last third of pregnancy. IGF-II was undetectable in pregnant and non-pregnant rats. IGF-binding protein (IGFBP) concentrations, measured as high molecular mass activity in the IGF-I RIA and the IGF-II RRA of acid column fractions, paralleled the changes observed with IGF-I. Western ligand blot analysis of serum from non-pregnant rats revealed a 40–50 kDa IGFBP aligning with IGFBP-3, a smaller 28–30 kDa doublet and 24 kDa IGFBP. Serum from rats in late pregnancy lacked IGFBP-3, whereas the smaller IGFBP persisted during late pregnancy. IGFBP-3 reappeared in postpartum animals. The fall in serum IGF-I is consistent with a maternal catabolic state during late pregnancy which may maximize substrate availability for the developing fetus. Journal of Endocrinology (1990) 127, 383–390

Dexamethasone ester treatment alters insulin-like growth factor-I, its binding proteins and thyroid status in finishing calves

2000 ◽  
Vol 80 (2) ◽  
pp. 329-335 ◽  
Author(s):  
C. Bertozzi ◽  
D. Portetelle ◽  
S. Massart ◽  
A. Prandi ◽  
V. Darras ◽  
...  
Keyword(s):  
Growth Factor ◽  
Thyroid Hormones ◽  
Mrna Expression ◽  
Binding Proteins ◽  
Hepatic Tissue ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Igfbp 3

To improve carcass quality in finishing calves, some breeders use preparations containing corticoids alone or in association with other growth promoters. We have investigated the effects of dexamethasone treatment on insulin-like growth factor-I (IGF-I), IGF-binding proteins (IGFBP-2 and 3) and thyroid hormones (T3, T4, free T4). Limousine male calves were allocated to a control group (C) (n = 18) and a group (n = 18) that received dexamethasone esters (DEX). Blood and hepatic tissue samples were collected at slaughtering. Thyroid hormones and IGF-I plasma levels were measured by RIA and IGFBPs were evaluated by immunoblotting. Hepatic type I 5′deiodinase (5′D-I) activity was determined by enzyme assay and hepatic expression of mRNA for GH receptor, IGF-I, IGFBP-2, IGFBP-3 and type I deiodinase (D-I) was evaluated by dot blot analysis. Plasma IGF-I and IGFBP-3 levels were reduced by the DEX treatment (P < 0.001 and P < 0.01, respectively) while IGFBP-2 was unaffected. Significant plasma changes for IGF-I and IGFBP-3 were not corroborated by hepatic mRNA levels, for which only a slight non-significant decrease was noted. Growth hormone receptor mRNA expression was increased after treatment (P < 0.01). T3 plasma level was higher in DEX animals (P < 0.05) than in C calves. Finally, treatment increased 5′D-I activity in the hepatic tissue (P < 0.001) and seemed to also affect D-I mRNA expression (P = 0.1). In conclusion, dexamethasone ester injection in calves altered some of their endocrinological parameters; this could explain the catabolic action of corticoids in the bovine species. Key words: Calves, corticoids, IGF-I, IGFBPs, thyroid axis

Pharmacokinetics of insulin-like growth factor I in hypopituitarism: correlation with binding proteins

1999 ◽  
Vol 277 (4) ◽  
pp. E579-E584 ◽  
Author(s):  
Nelly Mauras ◽  
Valerie Quarmby ◽  
Duane C. Bloedow
Keyword(s):  
Growth Factor ◽  
Half Life ◽  
Binding Proteins ◽  
Hormone Deficiency ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Normal Absorption ◽  
Igf I ◽  
Growth Factor I ◽  
Igfbp 3

We investigated the pharmacokinetics of recombinant human insulin-like growth factor I (rhIGF-I) in growth hormone deficiency (GHD). Nine GHD adults [age 25 ± 3 (SE) yr] received rhIGF-I (60 μg/kg sc) twice, 10 h apart, and blood was sampled over 24 h. IGF-I and free IGF-I concentrations increased, whereas IGF binding protein 3 (IGFBP-3) and acid labile subunit (ALS) were unchanged during treatment. There was no correlation between absorption or terminal half-life of IGF-I and IGFBP-3 or ALS, but negative correlations with IGF-I clearance (CL/F) and volume of distribution (V/F). Positive correlations between both IGFBP-3 and ALS and IGF-I maximal concentration (Cmax) and time of Cmax( T max) were observed. Compared with normal individuals studied similarly (using 80 μg/kg), GHD subjects showed a normal absorption half-life, a faster elimination half-life, lower Cmax, yet normal T maxand V/F. In conclusion, GHD is associated with normal absorption and distribution of IGF-I yet faster elimination kinetics. Additionally, IGFBP-3 and ALS concentrations modulate the peak concentrations of IGF-I achieved and correlate reciprocally with its V/F and CL/F, underscoring the critical importance of binding proteins in modulating the bioavailability of IGF-I in vivo in humans.

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