Insulin-like growth factor I and II in 14 animal species and man as determined by three radioligand assays and two bioassays

1987 ◽  
Vol 114 (1) ◽  
pp. 107-112 ◽  
Author(s):  
Ines Zangger ◽  
Jürgen Zapf ◽  
E. Rudolf Froesch
Keyword(s):  
Growth Factor ◽  
Animal Species ◽  
Mammalian Species ◽  
Cross Reactivity ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Fat Cell ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Abstract. Insulin-like growth factor I and II (IGF I and II) were determined by five different assays in human serum, in the sera of ten mammalian species and in chicken, turtle, and frog serum. Sera of all tested mammals contain two different IGFs corresponding to human immunoreactive IGF I and receptor reactive IGF II. Receptor reactive IGF II of most animal species does not show significant cross-reactivity in the RIA for human IGF II. IGF activity was also detected in sera of non-mammals, such as chicken and turtles, but not in frog serum. The IGF values obtained with the different assay system corresponded rather well: there is a good correlation between the values obtained in the protein binding and the fat cell assay, and between the results of the latter assays and the sum of immunoreactive IGF I and receptor reactive IGF II. The results suggest that those regions in the IGF I and II molecules which are responsible for reactivity with the type I IGF and the insulin receptor have not essentially changed during evolution. Similarly, the C-region, which mainly determines the immunological properties of IGFs, appears to have remained relatively constant in the IGF I, but not in the IGF II molecule.

Purification, amino acid sequences and assay cross-reactivities of porcine insulin-like growth factor-I and -II

1989 ◽  
Vol 122 (3) ◽  
pp. 681-687 ◽  
Author(s):  
G. L. Francis ◽  
P. C. Owens ◽  
K. A. McNeil ◽  
J. C. Wallace ◽  
F. J. Ballard
Keyword(s):  
Amino Acid ◽  
Growth Factor ◽  
Mammalian Species ◽  
Cross Reactivity ◽  
Porcine Insulin ◽  
Amino Acid Sequences ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

ABSTRACT Porcine insulin-like growth factor-I (IGF-I) and IGF-II have been characterized to help define the roles of these peptides in the growth process. The amino acid sequence of porcine IGF-I was found to be identical to the human and bovine peptides. Porcine IGF-II was more similar to human IGF-II than to forms of this growth factor in other mammalian species, differing only in the replacement of asparagine for serine at residue 36. In a biological assay that measures the stimulation of protein synthesis in rat L6 myoblasts, porcine IGF-I was approximately ninefold more potent than porcine IGF-II or bovine IGF-II, while recombinant human IGF-I and IGF-II had half the potency of the respective natural peptides. Porcine and recombinant human IGF-I showed essentially equal competition for binding in a human IGF-I radioimmunoassay while between 0·6 and 1·5% cross-reactivity was observed with human, bovine or porcine IGF-II. A receptor assay for IGF-II demonstrated similar potencies for the three IGF-II peptides, while the cross-reactivity of recombinant human IGF-I was only 0·05%. Porcine IGF-I exhibited a higher cross-reactivity, presumably due to very slight contamination with IGF-II. Journal of Endocrinology (1989) 122, 681–687

scholarly journals Purified hybrid insulin/insulin-like growth factor-I receptors bind insulin-like growth factor-I, but not insulin, with high affinity

1993 ◽  
Vol 290 (2) ◽  
pp. 419-426 ◽  
Author(s):  
M A Soos ◽  
C E Field ◽  
K Siddle
Keyword(s):  
Monoclonal Antibody ◽  
Growth Factor ◽  
Insulin Receptors ◽  
Beta Subunit ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf Receptors ◽  
Igf I ◽  
Growth Factor I

Hybrid insulin/insulin-like growth factor-I (IGF-I) receptors have previously been described in human placenta, but it has not been possible to study their properties in the presence of classical insulin receptors and type I IGF receptors. To facilitate the purification of hybrids, we produced an anti-peptide monoclonal antibody IGFR 1-2, directed against the C-terminal peptide of the type I IGF receptor beta-subunit. The antibody bound native human and rat type I IGF receptors, and reacted specifically with the beta-subunit on immunoblots. Solubilized placental microsomal membranes were depleted of classical type I IGF receptors by incubation with an immobilized monoclonal antibody IGFR 24-55, which reacts well with type I receptors but very poorly with hybrid receptors. Residual hybrid receptors were then isolated by incubation with immobilized antibody IGFR 1-2, and recovered by elution with excess of synthetic peptide antigen. Binding properties of hybrids were compared with those of immuno-affinity-purified insulin receptors and type I IGF receptors, by using the radioligands 125I-IGF-I and 125I-insulin. Hybrids bound approx. 20 times as much 125I-IGF-I as 125I-insulin at tracer concentrations (approx. 0.1 nM). The binding of 125I-insulin, but not 125I-IGF-I, to hybrids increased after treatment with dithiothreitol to reduce disulphide bonds between the alpha-subunits. Hybrids behaved very similarly to type I receptors with respect to the inhibition of 125I-IGF-I binding by unlabelled IGF-I and insulin. By contrast, the affinity of hybrids for insulin was approx. 10-fold lower than that of classical insulin receptors, as assessed by inhibition of 125I-insulin binding by unlabelled hormone. It is concluded that the properties of insulin receptors, but not IGF receptors, are markedly affected by assembly as hybrid compared with classical structures, and that hybrids are more likely to be responsive to IGF-I than insulin under physiological conditions.

scholarly journals Effects of Short-Term Insulin-Like Growth Factor-I (IGF-I) or Growth Hormone (GH) Treatment on Bone Metabolism and on Production of 1,25-Dihydroxycholecalciferol in GH-Deficient Adults1

1998 ◽  
Vol 83 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Tarcisio Bianda ◽  
Yvonne Glatz ◽  
Roger Bouillon ◽  
Ernst Rudolf Froesch ◽  
Christoph Schmid
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Bone Formation ◽  
Bone Turnover ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Gh Treatment ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Administration of insulin-like growth factor-I (IGF-I) or growth hormone (GH) is known to stimulate bone turnover and kidney function. To investigate the effects of IGF-I and GH on markers of bone turnover, eight adult GH-deficient patients (48 ± 14 yr of age) were treated with IGF-I (5 μg/kg/h in a continuous sc infusion) and GH (0.03 IU/kg/daily sc injection at 2000 h) in a randomized cross-over study. We monitored baseline values for three consecutive days before initiating the five-day treatment period, as well as the wash-out period of ten weeks. Serum osteocalcin, carboxyterminal and aminoterminal propeptide of type I procollagen (PICP and PINP, respectively) increased significantly within 2–3 days of both treatments (P < 0.02) and returned to baseline levels within one week after the treatment end. The changes in resorption markers were less marked as compared with formation markers. Total 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) rose significantly, whereas PTH and calcium levels remained unchanged during either treatment. Conclusions: Because the rapid increase in markers of bone formation was not preceded by an increase in resorption markers, IGF-I is likely to stimulate bone formation by a direct effect on osteoblasts. Moreover, because PTH, calcium, and phosphate remained unchanged, IGF-I appears to stimulate renal 1α-hydroxylase activity in vivo.

scholarly journals Age-related changes in effects of insulin-like growth factor I on human osteoblast-like cells

1997 ◽  
Vol 324 (3) ◽  
pp. 753-760 ◽  
Author(s):  
Patricia Y. d'AVIS ◽  
Chester R. FRAZIER ◽  
Jay R. SHAPIRO ◽  
Neal S. FEDARKO
Keyword(s):  
Extracellular Matrix ◽  
Steady State ◽  
Growth Factor ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Human Osteoblast ◽  
Factor I ◽  
Igf I ◽  
Age Dependent ◽  
Growth Factor I

The role of insulin-like growth factor I (IGF-I) in extracellular matrix metabolism was studied in both proliferating and confluent human osteoblast-like cultures derived from donors of different ages. In proliferating cultures, recombinant human (rh)IGF-I was found to increase the incorporation of [3H]thymidine in a dose- and age-dependent manner. To study cell proliferation dynamically, continuous growth curves with and without rhIGF-I were modelled by a modified logistic function. Increasing doses of rhIGF-I decreased the lag time and maximal growth rates, whereas plateau values decreased only at the highest dose (100 ng/ml). In post-proliferative cell strains, rhIGF-I (0.1–100 ng/ml) increased levels of type I collagen, biglycan and decorin, and to a smaller extent fibronectin and thrombospondin, whereas it decreased the levels of hyaluronan and a versican-like proteoglycan when protein and proteoglycan metabolism were followed by steady-state radiolabelling with [3H]proline, [3H]glucosamine or [35S]sulphate. These responses to rhIGF-I were found to be age-dependent, with osteoblast-like cells derived from younger patients being more responsive to rhIGF-I. When extracellular matrix turnover was analysed by pulse–chase experiments, rhIGF-I had no effect. The steady-state levels of collagen, decorin, hyaluronan and a versican-like proteoglycan for bone cells treated with rhIGF-I on day 7 in culture were equivalent to levels of these matrix components in untreated osteoblasts grown for 14 days. These results are consistent with rhIGF-I's altering cellular proliferative capacity and matrix synthesis, causing a change in the osteoblast differentiated state.

Insulin-like growth factor-I and type I insulin-like growth factor receptor in 85% O2-exposed rat lung

1996 ◽  
Vol 271 (1) ◽  
pp. L139-L149 ◽  
Author(s):  
R. N. Han ◽  
V. K. Han ◽  
S. Buch ◽  
B. A. Freeman ◽  
M. Post ◽  
...  
Keyword(s):  
Growth Factor ◽  
Growth Factor Receptor ◽  
Airway Hyperreactivity ◽  
Alveolar Epithelial Cells ◽  
Northern Analysis ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

The expression of insulin-like growth factor I (IGF-I) and insulin-like growth factor II (IGF-II) was studied in the lungs of adult rats exposed to air or 85% O2, using Northern analysis, in situ hybridization, and immunohistochemistry. Distribution of the type I insulin-like growth factor receptor (IGF-IR) was assessed by immunohistochemistry. IGF-I, but not IGF-II, was localized to airway epithelium, while IGF-IR was localized to perivascular and peribronchial cells, in the lungs of animals breathing air. IGF-II mRNA did not increase with exposure to 85% O2, but IGF-II was localized to sites of perivascular edema and to occasional peribronchial cells. A widespread increase in IGF-I mRNA and peptide was seen after both a 6-day and a 14-day exposure to O2, with maximal expression in the airway and alveolar epithelium, and lesser expression in interstitial cells. After 6 days in 85% O2, increased IGF-IR immunoreactivity was localized to both perivascular and peribronchial cells and to endothelial cells. By 14 days in 85% O2, IGF-IR immunoreactivity was also localized to alveolar epithelial cells. The distribution of IGF-IR immunoreactivity was consistent with a paracrine role for IGF-I in O2-mediated pulmonary hypertension and airway hyperreactivity, by mediating smooth muscle cell hyperplasia, as well as a role in endothelial cell repair and late pneumocyte hyperplasia. The relative insensitivity of IGF-IR immunohistochemistry did not allow us to identify cells with low abundance IGF-IR, and potential cellular targets for IGF-I actions after O2-exposure may be even more extensive than those recognized here.

scholarly journals Insulin-like growth factor-I stimulates differentiation of ATII cells to ATI-like cells through activation of Wnt5a

2013 ◽  
Vol 305 (3) ◽  
pp. L222-L228 ◽  
Author(s):  
Manik C. Ghosh ◽  
Vijay Gorantla ◽  
Patrudu S. Makena ◽  
Charlean Luellen ◽  
Scott E. Sinclair ◽  
...  
Keyword(s):  
Growth Factor ◽  
Culture Media ◽  
Alveolar Type ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Differentiation Process ◽  
Factor I ◽  
Complex Biological Process ◽  
Igf I ◽  
Growth Factor I

Alveolar type II (ATII) epithelial cells play a crucial role in the repair and remodeling of the lung following injury. ATII cells have the capability to proliferate and differentiate into alveolar type I (ATI) cells in vivo and into an ATI-like phenotype in vitro. While previous reports indicate that the differentiation of ATII cells into ATI cells is a complex biological process, the underlying mechanism responsible for differentiation is not fully understood. To investigate factors involved in this differentiation in culture, we used a PCR array and identified several genes that were either up- or downregulated in ATI-like cells ( day 6 in culture) compared with day 2 ATII cells. Insulin-like growth factor-I (IGF-I) mRNA was increased nearly eightfold. We found that IGF-I was increased in the culture media of ATI-like cells and demonstrated a significant role in the differentiation process. Treatment of ATII cells with recombinant IGF-I accelerated the differentiation process, and this effect was abrogated by the IGF-I receptor blocker PQ401. We found that Wnt5a, a member of the Wnt-Frizzled pathway, was activated during IGF-I-mediated differentiation. Both protein kinase C and β-catenin were transiently activated during transdifferentiation. Knocking down Wnt5a using small-interfering RNA abrogated the differentiation process as indicated by changes in the expression of an ATII cell marker (prosurfactant protein-C). Treatment of wounded cells with either IGF-I or Wnt5a stimulated wound closure. These results suggest that IGF-I promotes differentiation of ATII to ATI cells through the activation of a noncanonical Wnt pathway.

scholarly journals Metabolic response of sheep skin to a chronic infusion of a variant of insulin-like growth factor I

1995 ◽  
Vol 308 (2) ◽  
pp. 411-418 ◽  
Author(s):  
J E Hocking Edwards ◽  
S K Khalaf ◽  
B R Sinclaire ◽  
J Lee ◽  
C G Prosser ◽  
...  
Keyword(s):  
Amino Acids ◽  
Growth Factor ◽  
Plasma Concentrations ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Wool Production ◽  
Factor I ◽  
Igf I ◽  
Wool Follicle ◽  
Growth Factor I

The effects of a chronic (21-day) skin infusion of a variant of insulin-like growth factor I (IGF-I) (long-Arg3-IGF-I; LR3IGF-I) on short-term (48 h) responses of skin metabolism and 21-day plasma hormone concentration, wool-follicle characteristics and wool production were investigated in well-fed castrated Romney sheep. A bilateral arteriovenous preparation was used to infuse LR3IGF-I continuously into the skin on one abdominal flank and saline into the other abdominal flank of six sheep; a further six sheep had one flank infused with saline (controls). LR3IGF-I caused an initial (4-24 h) reduction in the plasma concentrations of amino acids, especially tyrosine, valine and lysine, and, after 24 h, significant (P < 0.05) reductions in blood oxygen and plasma glucose concentrations. After 4 h of LR3IGF-I infusion, there was a significant increase in blood flow (P < 0.05) and oxygen uptake (P < 0.05), and net uptake of amino acids [which was significant (P < 0.05) for valine and phenylalanine] by the LR3IGF-I-infused skin was increased. Total uptake of phenylalanine for skin protein synthesis, measured using [3H]phenylalanine uptake, was also significantly increased after 4 and 24 h of infusion. After 48 h of infusion all LR3IGF-I-dependent measurements of metabolic parameters had fallen to preinfusion values. By day 7 of the 21-day infusion there was a significant (P < 0.05) decrease in circulating endogenous IGF-I in plasma of treated sheep compared with that of control sheep, followed by a significant (P < 0.05) increase between day 7 and 21. Plasma insulin levels followed a similar pattern. There was no change at any stage of infusion in IGF-binding proteins in the plasma of the two LR3IGF-I-infused sheep tested, and it is concluded that LR3IGF-I caused a down-regulation of the type-I IGF-I receptors followed by a rise in endogenous IGF-I concentration consequent on lack of feedback regulation. After 21 days of infusion there was no effect of LR3IGF-I on wool-follicle-bulb-cell mitotic rate, bulb diameter or wool production.(ABSTRACT TRUNCATED AT 400 WORDS)

Immunohistochemical localisation of growth hormone (GH), GH receptor (GHR), insulin-like growth factor I (IGF-I) and type I IGF-I receptor, and gene expression of GH and GHR in rat pre-antral follicles

Zygote ◽  
2002 ◽  
Vol 10 (1) ◽  
pp. 85-94 ◽  
Author(s):  
J. Zhao ◽  
M.A.M. Taverne ◽  
G.C. van der Weijden ◽  
M.M. Bevers ◽  
R. van den Hurk
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Growth Factor ◽  
Follicular Development ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Antral Follicles ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

We previously demonstrated that the development of cultured rat pre-antral follicles is stimulated by growth hormone (GH) and insulin-like growth factor-I (IGF-I) and that the mRNA of IGF-I and type I IGF receptor (IGFR) is present in the oocyte and wall of these follicles. To gain a closer insight into the regulation of early folliculogenesis by GH and IGF-I, the present study investigated the gene expression of GH and GHR mRNA in isolated oocytes and follicular wall cells of pre-antral follicles, using reverse transcriptase polymerase chain reaction, and the localisation of immunoreactive IGF-I, IGFR, GH and GHR proteins in ovarian sections of 10-day-old rats. GH was detected in oocytes and follicular wall tissue of pre-antral follicles, whereas expression of the GH mRNA was absent. The GHR mRNA was present in follicular wall tissue and not in the oocyte, while positive immunostaining for GHR was observed in all cells of the pre-antral follicles. Immunoreactive IGF-I and IGFR was also visible in the pre-antral follicles, especially in the oocytes. In conclusion, the data show that the previously demonstrated local gene expression of IGF-I and IGFR in oocytes and their enveloping follicular cells also leads to translation, which points to the involvement of intrafollicular IGF-I in early follicular development. The presence of the GHR mRNA and the GHR and GH proteins in pre-antral follicles in the absence of ovarian GH mRNA suggest a direct effect of systemic GH on early follicular development.

Developmental changes in chicken and turkey insulin-like growth factor-I (IGF-I) studied with a homologous radioimmunoassay for chicken IGF-I

1994 ◽  
Vol 142 (2) ◽  
pp. 225-234 ◽  
Author(s):  
J P McMurtry ◽  
G L Francis ◽  
F Z Upton ◽  
G Rosselot ◽  
D M Brocht
Keyword(s):  
Growth Factor ◽  
Cross Reactivity ◽  
Developmental Changes ◽  
Insulin Like Growth Factor ◽  
Response Curves ◽  
Igf Binding Proteins ◽  
Factor I ◽  
Tissue Extracts ◽  
Igf I ◽  
Growth Factor I

Abstract The development of a homologous radioimmunoassay (RIA) for chicken insulin-like growth factor-I (cIGF-I) and its use to investigate the developmental changes in IGF-I in the chicken and turkey is described. A doubleantibody RIA has been developed using recombinantly derived cIGF-I as antigen, radiolabelled tracer and standard. The resulting immunoassay has a minimum detection limit of 0·035 ng and effective dose of 2·5 ng. Dose–response curves of chicken and turkey plasma and tissue extracts were parallel with cIGF-I standard. The antiserum is specific for IGF-I as no cross-reactivity with chicken IGF-II, insulin, glucagon, gastrin or avian pancreatic polypeptide was observed. We have also established that acid/ethanol extraction of chicken and turkey plasma reduced possible interference of IGF-binding proteins (IGFBPs) in the RIA. Comparison of IGF-I immunoactivity in unextracted and acid/ethanol-extracted samples following gel filtration under acidic and neutral conditions indicates that the cIGFBPs may be acid-labile. Analyses of samples from growing chickens and turkeys using the homologous avian reagents revealed higher IGF-I concentrations than if the IGF were quantified using heterologous mammalian-derived reagents. A similar pattern was observed when tissue extracts were assayed for IGF-I content. The application of the homologous RIA to monitor blood and tissue IGF-I levels during embryonic development and posthatch growth in avian species will provide more accurate comparisons of results from studies on the role of IGF-I in growth and metabolism of domestic birds. Journal of Endocrinology (1994) 142, 225–234

Sign in / Sign up

Export Citation Format

Share Document