scholarly journals Role of insulin-like growth factor binding proteins in limitation of IGF-I degradation into the N-methyl-d-aspartate receptor antagonist GPE: evidence from gonadotrophin-releasing hormone secretion in vitro at two developmental stages

1999 ◽  
Vol 847 (2) ◽  
pp. 247-252 ◽  
Author(s):  
Jean-Pierre Bourguignon ◽  
Arlette Gérard
Keyword(s):  
Growth Factor ◽  
Receptor Antagonist ◽  
Binding Proteins ◽  
Developmental Stages ◽  
Hormone Secretion ◽  
Aspartate Receptor ◽  
Igf I ◽  
Gonadotrophin Releasing Hormone

Secretion of insulin-like growth factor-I (IGF-I) and IGF-binding proteins from bovine mammary tissue in vitro

1991 ◽  
Vol 128 (2) ◽  
pp. 219-228 ◽  
Author(s):  
P. G. Campbell ◽  
T. C. Skaar ◽  
J. R. Vega ◽  
C. R. Baumrucker
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Conditioned Media ◽  
Mammary Tissue ◽  
Igf Binding Proteins ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Bovine Mammary Tissue

ABSTRACT In vitro, insulin-like growth factor-I (IGF-I) promotes both growth and development of bovine mammary tissue. In vivo, the effects of IGF-I may encompass endocrine, paracrine or autocrine mediation. We addressed the possibility of paracrine/autocrine effects of IGF-I in the mammary gland by examining the in-vitro secretion of IGF-I and IGF-binding proteins (IGFBPs) from bovine mammary tissue. Bovine mammary explants from pregnant non-lactating and lactating non-pregnant animals were found to synthesize and secrete IGF-I and IGFBPs. Mammary acini cultures, representative of mammary secretory epithelia, secreted both IGF-I and IGFBP, but synthesized only IGFBP. Concentrations of IGF-I in conditioned media from explants were 1·54 and 0·72 fmol/μg DNA for pregnant and lactating animals respectively. Concentrations of IGFBPs in conditioned media from explants were similar for both physiological states at 2529 pmol 125I-labelled IGF-I bound/pg DNA. Ligand/Western blotting procedures identified four IGFBPs of 29, 33, 37 and 44 kDa for acini cultures and five IGFBPs of 28, 31, 36, 44 and 46 kDa for explant cultures. Similar affinities for IGF-I and IGF-II were shown by IGFBP, using 125I-labelled recombinant human IGF-I as the competing ligand (median effective dose (ED50) of 0·085 pmol). When 125I-labelled bovine IGF-II was used as the ligand, only bovine IGF-II (ED50 of 0·25 pmol) inhibited binding. The addition of prolactin, insulin and cortisol, with or without GH, did not affect secretion of either IGF-I or IGFBP. This report describes the ability of normal mammary tissue to synthesize and secrete IGF-I and IGFBPs. Journal of Endocrinology (1991) 128, 219–228

Production of insulin-like growth factor I (IGF-I) and IGF-binding proteins by rat intestinal stromal cells in vitro

1998 ◽  
Vol 54 (2) ◽  
pp. 158-166
Author(s):  
R. G. MacDonald ◽  
R. H. McCusker ◽  
D. J. Blackwood ◽  
J. A. Vanderhoof ◽  
J. H. Y. Park
Keyword(s):  
Growth Factor ◽  
Stromal Cells ◽  
Binding Proteins ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Growth Factor I

Protein glycation: its role in the changes induced by diabetes in the properties of the serum insulin-like growth factor-I binding proteins

1991 ◽  
Vol 131 (1) ◽  
pp. 33-38 ◽  
Author(s):  
A. M. Cortizo ◽  
J. J. Gagliardino
Keyword(s):  
Growth Factor ◽  
Glucose Concentration ◽  
Binding Proteins ◽  
Binding Capacity ◽  
Diabetic Rats ◽  
Protein Glycation ◽  
Oral Glucose ◽  
Insulin Like Growth Factor ◽  
Igf I

ABSTRACT The purpose of this work was to study the effect of diabetes on 125I-labelled insulin-like growth factor (IGF) binding to specific serum binding proteins (IGFBPs) and the possible role of protein glycation in such an effect. Accordingly, ligand blotting and fructosamine assays were performed in serum samples from diabetic and non-diabetic eSS rats as well as in samples of normal rat serum previously incubated with different concentrations of glucose. IGFBPs with molecular weights of 24, 30 and 40 kDa were identified in samples from diabetic and non-diabetic rats. 125I-Labelled IGF-I binding to each of these fractions increased significantly in the serum of diabetic rats. IGF-I binding to IGFBP-40 increased significantly as a function of the degree of glycation of serum proteins. Conversely, the increased binding of IGFBP-24 and IGFBP-30 was related only to the glucose concentration attained at 120 min during the oral glucose tolerance test. Glycation of proteins of normal serum and the binding of labelled IGF-I increased as a function of glucose concentration in the incubation media. In these in-vitro glycated normal sera, only the binding to IGFBP-40 increased significantly; this increase was closely related to the amount of protein glycation. No clear and reproducible changes occurred with the binding of 125I-labelled IGF-I to IGFBP-24 and IGFBP-30 fractions. These results confirm the increase in the binding capacity of IGFBPs reported in diabetic animals. They also show that the increase in IGF-I binding to each IGFBP fraction is regulated by a different mechanism; whereas protein glycation induces changes in IGFBP-40, this mechanism does not affect the binding properties of the other two IGFBPs. The increased binding of IGFBP might affect the availability of free IGF-I, and the consequent alterations in IGF-I-dependent metabolic processes could explain the role of this growth factor in the pathogenesis of chronic complications of diabetes. Journal of Endocrinology (1991) 131, 33–38

The involvement of insulin-like growth factor-I in local control of steroidogenesis and DNA synthesis of Leydig and non-Leydig cells in the rat testicular interstitium

1993 ◽  
Vol 138 (1) ◽  
pp. 107-114 ◽  
Author(s):  
A. Moore ◽  
I. D. Morris
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Leydig Cell ◽  
Interstitial Fluid ◽  
Binding Proteins ◽  
Interstitial Cells ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I

ABSTRACT Insulin-like growth factor-I (IGF-I) peptide, receptors and binding proteins are present in the rodent testis, which strongly implies that IGF-I has one or more testicular functions. In the present study we provide further information to support the concept that IGF-I is an important local mediator in the testis. High concentrations of IGF-I were measurable in interstitial fluid by radioimmunoassay, and IGF-I-binding proteins (IGFBPs) were readily detectable in interstitial fluid by ligand blotting, the predominant type being IGFBP-2. In vitro, IGF-I bound to testicular interstitial cells which did not have 3β-hydroxysteroid dehydrogenase (3β-HSD) activity and which were resistant to ethane dimethanesulphonate treatment. In vitro, IGF-I receptor-mediated actions increased both steroidogenesis and DNA synthesis. Insulin stimulated DNA synthesis at concentrations appropriate to cross-react with the IGF-I receptor, and this effect was greater in a testicular interstitial Leydig cell-depleted cell population compared with a Leydig cell-enriched cell culture. Furthermore, combinations of epidermal growth factor or transforming growth factor -α together with insulin appeared to act synergistically, causing extremely large increases in [3 H]thymidine incorporation in the interstitial cells. These results support a paracrine and/or autocrine role for IGF-I in interstitial cell growth and development. Journal of Endocrinology (1993) 138, 107–114

Increased secretion of insulin-like growth factor-binding proteins and decreased secretion of insulin-like growth factor-II by muscle from growth-retarded neonatal rats

1991 ◽  
Vol 130 (1) ◽  
pp. 33-42 ◽  
Author(s):  
R. J. Frampton ◽  
H. A. Jonas ◽  
R. G. Larkins
Keyword(s):  
Growth Factor ◽  
Conditioned Medium ◽  
Binding Proteins ◽  
Muscle Protein ◽  
Growth Potential ◽  
Insulin Like Growth Factor ◽  
Neonatal Rats ◽  
Igf Binding Proteins ◽  
Igf I

ABSTRACT Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) may be important factors in the control of neonatal growth. We have examined the production, in vitro, of IGFBPs and IGFs by hindlimb skeletal muscle from normal and small-for-gestational age (SGA) neonatal rats. Conditioned medium was collected from muscle strips after incubation at 37 °C for 2 h in Ham's F-12 medium. The conditioned medium was subjected to acid-gel permeation chromatography to separate IGFBPs from IGFs. The binding of 125I-labelled IGF-I to IGFBPs from both control and SGA muscle was displaced equipotently by IGF-I and IGF-II and not at all by insulin. IGFBPs from control and SGA muscles bound IGF-I with comparable affinities (Kd = 0·071 and 0·069 nmol/l respectively). When IGF-II was used as tracer, neither IGF-I nor insulin competed for binding. Western ligand blots of IGFBPs in conditioned media from both control and SGA muscles showed three bands of radioactivity at molecular masses equivalent to 24, 30 and 40 kDa. When the release of IGFBPs by muscle tissue in vitro was quantified by measuring the number of IGF-I binding sites in acid-fractionated medium it was apparent that the muscles from SGA pups secreted significantly more IGFBPs (39·3±7·5 fmol/mg muscle protein per 2 h) than the muscles from control pups (17·8±2·7 fmol/mg protein per 2 h; P < 0·05). In contrast to the IGFBPs, more IGF activity was secreted by the muscles from the control pups (61·1±15·6 fmol/mg muscle protein per 2 h) than the muscles from the SGA pups (12·6±5·8 fmol/mg muscle protein per 2 h; P < 0·05). Analysis of the IGF activity with assays specific for IGF-I and IGF-II showed that both SGA and control muscles secreted predominantly IGF-II with approximately 10% of the total IGF activity measurable as IGF-I. This differential secretion of IGFBPs and IGFs may be associated with the reduced growth potential of the SGA neonate. Journal of Endocrinology (1991) 130, 33–42

scholarly journals Separation of Fast from Slow Anabolism by Site-specific PEGylation of Insulin-like Growth Factor I (IGF-I)

2011 ◽  
Vol 286 (22) ◽  
pp. 19501-19510 ◽  
Author(s):  
Friedrich Metzger ◽  
Waseem Sajid ◽  
Stefanie Saenger ◽  
Christian Staudenmaier ◽  
Chris van der Poel ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Site Specific ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Insulin-like growth factor I (IGF-I) has important anabolic and homeostatic functions in tissues like skeletal muscle, and a decline in circulating levels is linked with catabolic conditions. Whereas IGF-I therapies for musculoskeletal disorders have been postulated, dosing issues and disruptions of the homeostasis have so far precluded clinical application. We have developed a novel IGF-I variant by site-specific addition of polyethylene glycol (PEG) to lysine 68 (PEG-IGF-I). In vitro, this modification decreased the affinity for the IGF-I and insulin receptors, presumably through decreased association rates, and slowed down the association to IGF-I-binding proteins, selectively limiting fast but maintaining sustained anabolic activity. Desirable in vivo effects of PEG-IGF-I included increased half-life and recruitment of IGF-binding proteins, thereby reducing risk of hypoglycemia. PEG-IGF-I was equipotent to IGF-I in ameliorating contraction-induced muscle injury in vivo without affecting muscle metabolism as IGF-I did. The data provide an important step in understanding the differences of IGF-I and insulin receptor contribution to the in vivo activity of IGF-I. In addition, PEG-IGF-I presents an innovative concept for IGF-I therapy in diseases with indicated muscle dysfunction.

Insulin-like growth factor-binding proteins in tissue fluids from the lamb

1991 ◽  
Vol 129 (1) ◽  
pp. 59-68 ◽  
Author(s):  
A. P. D. Lord ◽  
A. A. Martin ◽  
P. E. Walton ◽  
F. J. Ballard ◽  
L. C. Read
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Specific Binding ◽  
Binding Protein ◽  
Extracellular Fluid ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Igf I ◽  
Acid Labile Subunit

ABSTRACT Heparinized samples of plasma, cerebrospinal fluid (CSF) and lymph from intestinal, prescapular and popliteal lymph nodes were collected from young lambs in order to characterize and compare the insulin-like growth factor-binding proteins (IGFBPs) in extracellular fluids with those from the circulation. Prior to collection and analysis, the superiority of heparin for plasma preparation was established over EDTA and citrate or the use of serum, according to the extent of IGF-I and IGF-II binding achieved in the high molecular mass IGFBP region in vitro. The IGFBPs were characterized by ligand blotting and competitive binding techniques using radiolabelled IGF-I, IGF-II and the truncated IGF analogue, des(1–3)IGF-I, as well as by ligand blotting of fractions after Superose 6 chromatography of incubations of fluids with labelled factors. This combined analysis demonstrated an IGF-II-specific binding protein at approximately 250 kDa that was present in plasma and each lymph type and presumably represented the soluble type-2 IGF receptor; a complex of 130 kDa containing 52 kDa and 46 kDa binding proteins that was labelled by all three IGF peptides was particularly evident in plasma and intestinal lymph and was probably a complex between IGFBP-3 and the acid-labile subunit; and a group of binding proteins that chromatographed as IGF complexes at approximately 50 kDa. This last group contained IGFBP bands of 52, 46, 35, 28 and 23·5 kDa in plasma and all lymphs as well as an IGF-II-specific band of 22 kDa in prescapular and popliteal lymphs. CSF differed qualitatively from plasma and lymph in that the 52/46 kDa IGFBP bands were undetectable in this fluid; the 35 kDa band was the predominant binding protein, and neither this nor the 28, 23·5 and 22 kDa proteins bound des(1–3)IGF-I to any significant extent. The 52,46 and 28 kDa bands in plasma and lymph did bind this ligand. Immunoblots using antisera against bovine IGFBP-2 showed binding at 35 kDa in all fluids as well as several bands at lower molecular masses. Taken together these results show not only marked differences in the binding protein profiles of sheep plasma, lymph and CSF, but both qualitative and quantitative differences between intestinal, prescapular and popliteal lymphs. We speculate that the differences between lymphs may result from tissuespecific release of binding proteins into extracellular fluid. Journal of Endocrinology (1991) 129, 59–68

From Mouse to Man: Redefining the Role of Insulin-Like Growth Factor-I in the Acquisition of Bone Mass

2003 ◽  
Vol 228 (3) ◽  
pp. 245-252 ◽  
Author(s):  
Shoshana Yakar ◽  
Clifford J. Rosen
Keyword(s):  
Growth Factor ◽  
Cell Function ◽  
Bone Cells ◽  
Bone Cell ◽  
Insulin Like Growth Factor ◽  
In Vivo Models ◽  
Igf I

The insulin-like growth factor system (IGF) has been linked to the process of bone acquisition through epidemiologic analyses of large cohorts and in vitro studies of bone cells. But the exact relationship between expression of IGF-I in bone and skeletal homeostasis or pathologic conditions, such as osteoporosis, remains poorly defined. Recent advances in genomic engineering have resulted in the development of better in vivo models to test the role of IGF-I during development and maintenance of the adult skeleton. It is now established that skeletal expression of IGF-I is critical for differentiative bone cell function. It may also be essential for the full anabolic effects of parathyroid hormone on trabecular bone and for some component of biomineralization. Evidence from conditional mutagenesis studies suggests that serum IGF-I may represent more than a storage depot or permissive factor during the final phase of skeletal acquisition. This work re-examines the original tenets of the “somatomedin hypothesis” in light of these newer mouse models and their remarkable skeletal phenotypes. The implications are far reaching and suggest that newer approaches for manipulating the IGF regulatory system may one day be useful as therapeutic adjuncts for the treatment of osteoporosis.

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