scholarly journals Effects of a single cleavage in insulin-like growth factors I and II on binding to receptors, carrier proteins and antibodies

1990 ◽  
Vol 266 (2) ◽  
pp. 513-520 ◽  
Author(s):  
J Jansen ◽  
S C van Buul-Offers ◽  
C M Hoogerbrugge ◽  
J L Van Den Brande
Keyword(s):  
Cell Membranes ◽  
Binding Proteins ◽  
Type I ◽  
Type Ii ◽  
Placental Cell ◽  
Basic Peptide ◽  
Receptor Sites ◽  
Common Receptor ◽  
Igf I ◽  
A Minor

Two somatomedin-like peptides were extracted from Cohn fraction IV of human plasma and brought to homogeneity: one focused at pH 7.8 and the other at pH less than 5.6. Each consisted of two peptide chains interlinked by disulphide bonds. The basic peptide was identical to insulin-like growth factor I (IGF-I) and had a single cleavage in the C-domain before Arg37 [IGF-I(Arg36cl)]. The acid peptide showed identity with IGF-II, with a cleavage in the B-domain before Arg30 [IGF-II(Ser29cl)]. The effects of these cleavages on the characteristics of binding to type I and type II receptor sites, to binding proteins and to antibodies was studied. Binding of IGF-I(Arg36cl) to antibodies directed against the B-domain or against the AD-domain of IGF-I was the same as IGF-I binding. Thus the cleavage does not influence these antigenic sites. In contrast, binding of IGF-I(Arg36cl) to the type I receptor on human and bovine placental cell membranes was markedly decreased compared with IGF-I binding. Binding to the insulin receptor on human placental cell membranes was slightly diminished, whereas the interaction with specific type II receptors on bovine placental cell membranes was unaffected. There was only a minor influence of the cleavage on the region involved in binding to binding proteins. The cleavage in IGF-II(Ser29cl) diminished binding to antibodies directed against the C-domain of IGF-II, compared with binding of IGF-II itself. Binding to receptors (type I and type II) was changed less profoundly. With 125I-labelled IGF-II(Ser29cl), less insulin was needed in order to obtain 50% displacement of the tracer compared with displacement of 125I-labelled IGF-II. The cleaved form of IGF-II probably has a greater affinity towards the common receptor population than does native IGF-II. Binding to binding proteins was not affected by the cleavage in IGF-II.

Characterization of specific insulin-like growth factor (IGF)-I and IGF-II receptors on cultured rabbit articular chondrocyte membranes

1989 ◽  
Vol 120 (2) ◽  
pp. 245-249 ◽  
Author(s):  
J. Jansen ◽  
S. C. van Buul-Offers ◽  
C. M. Hoogerbrugge ◽  
T. L. de Poorter ◽  
M. T. Corvol ◽  
...  
Keyword(s):  
Growth Factor ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Articular Chondrocyte ◽  
Reducing Conditions ◽  
Receptor Sites ◽  
Igf I ◽  
Typical Type ◽  
Liver Membranes ◽  
Placental Membranes

ABSTRACT The interaction of insulin-like growth factor (IGF)-I and IGF-II with specific type-I and -II receptor sites on rabbit articular chondrocyte membranes was studied. With labelled IGF-I as tracer, half-maximal displacement of the label was obtained with 1·4 ng IGF-I/ml and 22 ng IGF-II/ml. Using IGF-II as labelled peptide, 16 ng unlabelled IGF-II/ml and 200 ng IGF-I/ml were needed to inhibit the binding by 50%. Covalent cross-linking experiments revealed the presence of typical type-I (Mr 130 000 under reducing conditions) and type-II (Mr 260 000) receptor sites. In addition, with 125I-labelled IGF-II a very intense labelled band appeared at Mr > 300 000. This band was not found in mouse liver membranes and human placental membranes. Journal of Endocrinology (1989) 120, 245–249

Odour measurement - factors affecting olfactometry panel performance

1996 ◽  
Vol 34 (3-4) ◽  
pp. 549-556 ◽  
Author(s):  
P. J. Bliss ◽  
T. J. Schulz ◽  
T. Senger ◽  
R. B. Kaye
Keyword(s):  
Data Bank ◽  
Type I ◽  
Type Ii ◽  
Factors Affecting ◽  
Natural Logarithm ◽  
Odour Threshold ◽  
One Step ◽  
The Mean ◽  
A Minor ◽  
Over 40 Years

To identify factors affecting olfactometry panel performance in the measurement of environmental odours, a data bank of odour threshold measurements including 923 individual panel tests on environmental odours and 145 tests on standards were analysed statistically. There is an evident decrease in olfactory sensitivity to environmental odours with age. The group threshold tends to be one step lower for a 25 year increase in average age of panel members for Type I odours (piggery, feedlot, landfill and mushroom composting) and for 36 years increase for Type II odours (sewage and industrial coke works). The threshold for N-butanol tends to be 1 step lower for an increase of 15 years in age. People who are over 40 years old exhibited a greater variation than younger people. Although there was a minor gender difference in the sensitivity to butanol standard, it was not statistically significant (mean natural logarithm butanol threshold was 3.65 for males and 3.84 for females). Similar minor differences were exhibited in Confidence Index (CI), 1.72 for females (std. dev. 0.73) and 1.81 for males (std. dev. 0.77). Using “guess and correct” as criterion to determine individual thresholds in the forced choice olfactometry, the mean natural logarithm of ppb butanol is 1.365 lower than that for “certain and correct”. The standard deviation for “guess” and “certain” criteria were 1.093 and 0.911 respectively. The “certainty” criterion gave a better repeatability than the “guess” criterion.

Differential binding of 125I-IGF-I preparations to human fibroblast monolayers

1988 ◽  
Vol 118 (4) ◽  
pp. 513-520 ◽  
Author(s):  
C. A. Conover ◽  
P. Misra ◽  
R. L. Hintz ◽  
R. G. Rosenfeld
Keyword(s):  
Binding Sites ◽  
Human Fibroblast ◽  
Type I ◽  
Type Ii ◽  
Low Concentrations ◽  
Type I Igf Receptor ◽  
Igf I ◽  
Differential Binding ◽  
Igf Receptor ◽  
Binding Curves

Abstract. Specific, high affinity binding of 125I-IGF-I to the type I IGF receptor on human fibroblast monolayers was not altered by varying feeding schedules, serum lots, washing procedures, or incubation times and temperatures. However, markedly different competitive binding curves were obtained when different iodinated IGF-I preparations were used. Five of six radioligands bound preferentially to the type I IGF receptor on human fibroblast monolayers, with 50% displacement at 4–8 μg/l unlabelled IGF-I; with one radioligand a paradoxical 20–200% increase in 125I-IGF-I binding was observed at low concentrations of unlabelled IGF-I, while concentrations as high as 100 μg/l IGF-I failed to displace this radioligand. The latter binding pattern cannot be accounted for by 125I-IGF-I binding to the type II IGF receptor. These data indicate that various radioligands may have preferential affinities for different IGF-I binding sites on human fibroblast monolayers.

Relative occupation of type-I and type-II corticosteroid receptors in rat brain following stress and dexamethasone treatment: functional implications

1987 ◽  
Vol 115 (3) ◽  
pp. 459-467 ◽  
Author(s):  
J. M. H. M. Reul ◽  
F. R. van den Bosch ◽  
E. R. de Kloet
Keyword(s):  
Rat Brain ◽  
Plasma Concentrations ◽  
Striking Difference ◽  
Classical Type ◽  
Type I ◽  
Type Ii ◽  
Binding Studies ◽  
Receptor Sites ◽  
Basal Plasma

ABSTRACT The rat brain contains two receptor systems for corticosterone: the type-I corticosterone-preferring receptor and the classical type-II glucocorticoid receptor. The two receptor populations can be distinguished in binding studies with the 'pure' synthetic glucocorticoid 11β,17β-dihydroxy-6-methyl-17α (1-propynyl)-androsta-1,4,6-trione-3-one (RU 28362). In-vitro autoradiography and quantitative image analysis showed that the type-I receptor was localized almost exclusively in the hippocampus, whereas the type-II receptor extended throughout the brain, with the highest levels in the nucleus paraventricularis, nucleus supraopticus and in the thalamic, amygdaloid, hippocampal and septal regions. Unoccupied type-I and type-II receptor sites, as measured in vitro by cytosol binding of 3H-labelled steroids, displayed a large difference in the rate of appearance after adrenalectomy. The availability of type-I receptors exhibited a marked increase, reaching maximal levels within 4–7 h, and then remained constant until 2 weeks after adrenalectomy. The availability of type-II receptors did not change considerably during the first 24 h after adrenalectomy, but displayed a large increase in capacity during the subsequent 2 weeks. After adrenocortical activation as a consequence of exposure to a novel environment, plasma concentrations of corticosterone increased to reach a peak of 811 nmol/l after 30 min and attained the basal concentration (43 nmol/l) after 240 min. During this time, occupation of type-I receptors increased from 77·8% at 0 min to 97% at 30–60 min and then declined to 84·8% after 240 min. Occupation of the type-II receptors was 28·1% at 0 min, 74·5% after 30 min and 32·8% after 240 min. Injection of dexamethasone (25 μg/100 g body wt) at 08.00 h resulted in suppression of basal plasma concentrations of corticosterone and prevented the circadian-driven rise in circulating corticosterone. Occupation of type-I receptors did not change considerably as a result of injection of dexamethasone, but occupation of type-II receptors was markedly increased till 16.00 h compared with that after injection of vehicle. It was concluded that the type-I and type-II receptors are not only localized differently in the rat brain, but also exhibit a striking difference in occupation after manipulation of the pituitary-adrenocortical system. The data further support the concept of a type-I receptor-mediated tonic activating influence and a type-II receptor-mediated feedback action of corticosterone on brain function. J. Endocr. (1987) 115, 459–467

Stimulation of DNA synthesis in chicken muscle satellite cells by insulin and insulin-like growth factors: evidence for exclusive mediation by a type-I insulin-like growth factor receptor

1991 ◽  
Vol 128 (1) ◽  
pp. 35-NP ◽  
Author(s):  
M. J. Duclos ◽  
R. S. Wilkie ◽  
C. Goddard
Keyword(s):  
Growth Factors ◽  
Satellite Cells ◽  
Type I ◽  
Type Ii ◽  
Muscle Satellite Cells ◽  
Chicken Muscle ◽  
Type I Igf Receptor ◽  
Igf I ◽  
Igf Receptor ◽  
Insulin Like Growth Factors

ABSTRACT Insulin-like growth factors-I and -II (IGF-I and IGF-II) stimulate proliferation, differentiation, nutrient uptake and protein accretion in muscle cells. These effects are thought to be mediated through the type-I IGF receptor although a role for the type-II IGF receptor cannot be ruled out, since it has been found in most cells studied so far. Current evidence suggests that the chicken does not have a type-II IGF receptor and therefore provides a good model to study the function of IGF peptides. We have compared the effects of insulin and insulin-like growth factors on DNA synthesis with the binding of these peptides to receptors in primary chicken muscle satellite cells. Human IGF-I (hIGF-I), hIGF-II and porcine insulin increased thymidine incorporation into DNA by threefold in muscle satellite cells prepared from neonatal chickens. IGF-I and -II were almost equipotent, with half-maximum effective concentrations of 10 μg/l, and were 1000-fold more potent than insulin. A combination of maximum effective concentrations of all three peptides was not additive, suggesting that their effect was mediated by the same receptor. Receptor binding studies on satellite cells demonstrated the presence of specific IGF receptors. Human IGF-I inhibited the binding of 125I-labelled hIGF-I with a much higher potency than insulin, as usually observed for a type-I IGF receptor. However, unlabelled hIGF-II exhibited a higher potency than hIGF-I in displacing 125I-labelled hIGF-I. Affinity cross-linking of 125I-labelled hIGF-I and -II, followed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, showed that hIGF-I and -II bound to a receptor with the structural characteristics of a type-I IGF receptor and confirmed the lack of a type-II IGF receptor in these cells. The concentrations of IGF-I, -II and insulin required for biological action and to displace 125I-labelled hIGF-I binding were similar, and support the hypothesis that their effects on proliferation were mediated exclusively through a type-I IGF receptor. Journal of Endocrinology (1991) 128, 35–42

scholarly journals Augmented serum levels of the IGF-I/IGF-binding protein-3 ratio in pre-menopausal patients with type I breast cysts

2003 ◽  
pp. 177-184 ◽  
Author(s):  
PJ Enriori ◽  
CR Fischer ◽  
AE Etkin ◽  
RS Calandra ◽  
IA Luthy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Binding Protein ◽  
Type I ◽  
Type Ii ◽  
Healthy Women ◽  
Increased Risk ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

OBJECTIVE: Gross cystic disease (GCD) is the most common benign breast pathology. Although breast cysts are not considered pre-malignant lesions, an increased risk of breast cancer has been reported for patients with type I cysts (Na(+)/K(+)<3). Furthermore, an augmented IGF-I/IGF-binding protein-3 (IGFBP-3) ratio has been described in breast cancer patients. The objective was to evaluate serum IGF-I and binding protein concentrations of type I and type II cyst patients as compared with healthy women. METHODS: Twenty-four patients with type I cysts, 17 with type II cysts and 25 healthy women were evaluated. Serum IGF-I, IGFBP-3 and IGFBP-1 concentrations were measured by IRMA. RESULTS: IGF-I concentrations were significantly higher in sera from patients with type I cysts than in patients with type II cysts. A highly significant decrease of IGFBP-3, the major IGFBP, was found in patients with type I cysts with respect to healthy women, whereas no significant difference was evident between the different cyst types. The IGF-I/IGFBP-3 ratio, an estimate of biologically active IGF-I, was very significantly higher in patients with type I cysts than in both type II patients and healthy women. IGFBP-1 levels were significantly lower in patients with type I than in controls and type II cysts. The IGF-I/IGFBP-1 ratio was significantly higher in patients with type I cysts than in type II bearers and healthy women. Estrogen levels correlated with IGF-I in patients and controls. CONCLUSIONS: The enhanced levels of IGF-I/IGFBP-3 found in patients with type I cysts could eventually be associated with the increased risk of breast cancer described for this group.

scholarly journals Localization of binding sites for IGF-I, insulin and GH in the sow ovary

1999 ◽  
Vol 163 (2) ◽  
pp. 363-372 ◽  
Author(s):  
H Quesnel
Keyword(s):  
Granulosa Cells ◽  
Stromal Cells ◽  
Binding Sites ◽  
Binding Proteins ◽  
Cell Function ◽  
Type I ◽  
Thecal Cells ◽  
Igf I ◽  
Theca Externa ◽  
Theca Interna

Binding sites for IGF-I, insulin, and GH were localized by in situ binding of (125)I-labelled hormones to the different compartments of the sow ovary. Binding sites for IGF-I were detected in oocytes, granulosa and thecal cells of healthy and atretic follicles as well as in the antrum and the stroma. Competition of (125)I-labelled IGF-I with IGF-I, insulin and an analogue of IGF-I (Long R(3)IGF-I), which allowed discrimination between binding to binding proteins from binding to type-I receptors, suggested that type-I receptors were present in granulosa cells of healthy follicles, whilst binding in other compartments was mainly due to binding proteins. Binding of insulin was revealed in oocytes, granulosa and theca interna cells of healthy preantral and antral follicles, and, to a lesser extent, in theca externa and stromal cells, and was still observed in granulosa cells of atretic follicles. Labelling with (125)I-labelled bovine GH was demonstrated in oocytes, granulosa cells, theca interna cells, and, although less intense, in theca externa and stromal cells. It disappeared in granulosa cells during atresia. Binding sites for GH were detected at all follicular stages, from preantral to preovulatory stages, but the intensity of labelling in granulosa cells was more intense in preantral than in large follicles. These data support the participation of insulin, GH and IGF-I in oocyte maturation, follicular growth and stromal cell function in swine.

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