Developmentally Regulated Responses of Human Granulosa Cells to Insulin-Like Growth Factors (IGFs):IGF-I and IGF-II Action Mediated Via the Type-I IGF Receptor

1998 ◽  
Vol 83 (4) ◽  
pp. 1256-1259 ◽  
Author(s):  
D. S. Willis
Keyword(s):  
Growth Factors ◽  
Granulosa Cells ◽  
Type I ◽  
Developmentally Regulated ◽  
Human Granulosa Cells ◽  
Type I Igf Receptor ◽  
Igf I ◽  
Igf Receptor ◽  
Insulin Like Growth Factors

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 Developmentally Regulated Responses of Human Granulosa Cells to Insulin-Like Growth Factors (IGFs):IGF-I and IGF-II Action Mediated Via the Type-I IGF Receptor1

1998 ◽  
Vol 83 (4) ◽  
pp. 1256-1259 ◽  
Author(s):  
Debbie S. Willis ◽  
Helen D. Mason ◽  
Hazel Watson ◽  
Stephen Franks
Keyword(s):  
Growth Factors ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Similar Degree ◽  
Type I ◽  
Steroid Production ◽  
Human Granulosa Cell ◽  
Igf I ◽  
Igf Receptor ◽  
Insulin Like Growth Factors

In experimental animal models, insulin-like growth factors (IGFs) have been found to be more potent stimulators of ovarian function than insulin. In human theca cells, however, insulin, IGF-I, and IGF-II have similar effects on androgen production. The relative effects of insulin and IGFs on human granulosa cell steroidogenesis is unknown. Furthermore, it is unclear whether effects of IGF-II on steroidogenesis are mediated by the type-I or type-II IGF receptor. The effects of insulin, IGF-I, and IGF-II on human granulosa cell steroidogenesis were compared in vitro. As expected, insulin, IGF-I, and IGF-II enhanced steroidogenesis. Previously, IGF-II has been shown to enhance granulosa cell steroid production after insulin preincubation. In this study, an effect of IGF-II, independent of insulin priming, also was observed. In granulosa cell cultures from small antral follicles (≤13 mm), insulin and IGF-I stimulated steroid production to a similar degree, whereas IGF-II was less effective. In contrast, IGFs were more effective than insulin (IGF-I > IGF-II > insulin) in granulosa cells isolated from preovulatory follicles. IGF-I and IGF-II actions were mediated via the type-1 IGF receptor. The increased responsiveness of mature granulosa cells to IGFs may be an important mechanism by which granulosa cells increase their steroidogenic output in the preovulatory follicle.

Glucose regulation of the IGF response system in chondrocytes: induction of an IGF-I-resistant state

1999 ◽  
Vol 276 (4) ◽  
pp. R1164-R1171 ◽  
Author(s):  
K. M. Kelley ◽  
T. R. Johnson ◽  
J. Ilan ◽  
R. W. Moskowitz
Keyword(s):  
Glucose Concentration ◽  
Northern Analysis ◽  
Type I ◽  
Mrna Levels ◽  
Protein Levels ◽  
Receptor Mrna ◽  
Response System ◽  
Type I Igf Receptor ◽  
Igf I ◽  
Igf Receptor

Nonresponsiveness to the growth-stimulatory actions of insulin-like growth factor (IGF)-I in chondrocytes has been reported in a number of disease states associated with impaired glucose metabolism. Primary rabbit chondrocytes were investigated for changes in their IGF response system [type-I IGF receptor and IGF-binding protein (IGFBP) expression] and in their ability to mount a synthetic response to IGF-I [as35S-labeled proteoglycan ([35S]PG) production] in media containing varying ambient glucose concentrations. Whereas basal [35S]PG synthetic rate was unaffected by glucose concentration, synthetic responsiveness to IGF-I was lost in media containing <5 mmol/l glucose or in media containing a “diabetic” glucose concentration (25 mmol/l). IGFBP expression, as measured by Northern analysis of mRNA levels and Western ligand blotting of secreted protein levels, was not significantly altered in the different glucose media, nor were there any differences in the cell surface localization of IGFBPs as assessed by affinity cross-linking with 125I-labeled IGF-I, suggesting that IGFBPs do not induce the IGF-I resistance. The nonresponsiveness to IGF-I in reduced glucose occurred with 25–50% reductions in steady-state levels of IGF type-I receptor mRNA and protein. A significant correlation between IGF receptor mRNA level and synthetic response to IGF-I was observed between 0 and 10 mmol/l glucose concentrations, suggesting that the loss of responsiveness in reduced glucose is manifested at the level of transcription and/or receptor mRNA stability. In contrast, nonresponsiveness to IGF-I in chondrocytes in diabetic glucose concentrations occurred without changes in receptor mRNA and protein levels, suggesting that IGF-I resistance was due to post-ligand-binding receptor defects. It is proposed that IGF-I resistance in chondrocytes subjected to inappropriate glucose levels may constitute an important pathogenic mechanism in degenerative cartilage disorders.

scholarly journals Insulin-Like Growth Factor I (IGF-I) Receptor Overexpression Abolishes the IGF Requirement for Differentiation and Induces a Ligand-Dependent Transformed Phenotype in C2 Inducible Myoblasts*

Endocrinology ◽  
1997 ◽  
Vol 138 (12) ◽  
pp. 5210-5219 ◽  
Author(s):  
Magali Navarro ◽  
Bruno Barenton ◽  
Veronique Garandel ◽  
Juergen Schnekenburger ◽  
Henri Bernardi
Keyword(s):  
Growth Factors ◽  
Troponin T ◽  
Soft Agar ◽  
Specific Protein ◽  
Eukaryotic Expression ◽  
Type I ◽  
Phenotypic Differences ◽  
Human Type ◽  
Type I Igf Receptor ◽  
Igf I

Abstract Insulin-like growth factors (IGFs) stimulate both proliferation and differentiation of myogenic cell lines, and these actions are mostly mediated through the type I IGF receptor (type I IGF-R). To further investigate the role of this receptor in phenotypic characteristics of C2 murine myoblasts, we overexpressed the human type I IGF-R in the inducible clone of C2 cells, which requires IGFs in the differentiation medium to undergo terminal differentiation. Inducible myoblasts were transfected with either the eukaryotic expression vector pNTK or pNTK containing the human type I IGF-R complementary DNA, and we isolated two clones named Ind-Neo and Ind-R, respectively. Binding and autophosphorylation experiments indicate that Ind-R cells express about 10 times as much type I IGF-R compared with Ind-Neo control cells and that the transfected type I IGF-R is functional in Ind-R cells. We show that overexpression of the human type I IGF-R makes inducible myoblasts able to differentiate spontaneously, as assessed by expression of the myogenic transcription factors MyoD and myogenin, detection of the muscle-specific protein troponin T, and myotube formation. Moreover, when exposed to IGF-I, Ind-R cells lose contact inhibition, grow in the presence of a low level of growth factors and form colonies in soft agar, which is characteristic of a ligand-dependent transformed phenotype. It emerges from this study that 1) the type I IGF-R is strongly involved in the phenotypic differences between inducible and permissive cells with respect to the differentiation program; and 2) overexpression causes this receptor to act as a ligand-dependent transforming protein in muscle cells. We suggest that type I IGF-R abundance and level of activation may determine the efficiency of the autocrine mode of action of IGFs and discriminate their biological functions.

Immunoreactive and receptor-active insulin-like growth factor-I (IGF-I) and IGF-binding protein in blood plasma from the freshwater fish Macquaria ambigua (golden perch)

1993 ◽  
Vol 136 (2) ◽  
pp. 191-198 ◽  
Author(s):  
T. A. Anderson ◽  
L. R. Bennett ◽  
M. A. Conlon ◽  
P. C. Owens
Keyword(s):  
Binding Protein ◽  
Size Exclusion ◽  
Type I ◽  
Factor I ◽  
Type I Igf Receptor ◽  
Receptor Assay ◽  
Igf I ◽  
Igf Binding ◽  
Igf Receptor ◽  
Igf Binding Protein

ABSTRACT The presence of insulin-like growth factor-I (IGF-I)-related molecules and IGF-binding factors in blood from golden perch, Macquaria ambigua, an Australian native freshwater fish, was investigated. Serum was acidified to dissociate IGF and IGF-binding protein complexes that might be present, and fractionated by size-exclusion high-performance liquid chromatography at pH 2·8. Fractions were neutralized and their activities assessed by (i) an immunoassay for mammalian IGF-I which also detects chicken IGF-I but in which all known forms of IGF-II react very poorly, (ii) a receptor assay for IGF-II in which all known forms of IGF-I react poorly, and (iii) a type-I IGF receptor assay in which mammalian IGF-I and IGF-II polypeptides are almost equivalent. No IGF-II-like activity was detected. Three peaks of IGF-I-like activity were detected by IGF-I immunoassay and type-I IGF receptor assay. The major peak of activity was similar in molecular size to human IGF-binding protein-3, 45–55 kDa ('large IGF'), and a minor peak of activity which was similar in size to mammalian IGFs, 7·5 kDa. A third peak of activity was observed eluting at a time which indicates that it is a smaller molecule than any previously described IGF. The large IGF was temperature-sensitive, but was not a binding protein for 125I-labelled human IGF-I (hIGF-I). This material therefore was able to bind to anti-hIGF-I antibodies and to human type-I IGF receptors, and may represent the fish equivalent of mammalian prepro-IGFs. The two smallest forms of IGF activity identified by IGF-I radioimmunoassay and type-I radioreceptor assay following acidic size-exclusion chromatography were able to stimulate protein synthesis by L-6 myoblasts in culture, although large IGF did not. When fresh (but not frozen and thawed) golden perch serum was incubated with 125I-labelled hIGF-I and then fractionated by size-exclusion liquid chromatography at pH 7·4 through Sephadex G-100, the radioactivity became associated with a complex, intermediate in size between free IGF-I and the major IGF-binding protein in human serum. The association of 125I-labelled hIGF-I with the complex was inhibited by the presence of unlabelled hIGF-I in the incubation. These studies show that receptor-active, immunoreactive and bioactive IGF-I-like activity is present in golden perch serum, and demonstrate the presence of an IGF-I-binding factor in this species. Journal of Endocrinology (1993) 136, 191–198

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