The Type II Insulin-Like Growth Factor (IGF) Receptor Has Low Affinity for IGF-I Analogs: Pleiotypic Actions of IGFs on Myoblasts Are Apparently Mediated by the Type I Receptor*

Abstract. Binding of labelled IGF-I and IGF-II was studied to bovine, ovine and human placental cell membranes. The data show a preponderance of type I receptors in human placental membranes, and of type II receptors in ovine placental membranes, confirming reported data. In contrast, bovine placental membranes are rich in both type I and type II receptors. Therefore, the bovine placenta offers a good model for measuring specifically IGF-I (cross-reactivity with IGF-II 7%) and IGF-II (cross-reactivity with IGF-I 4%). By Scatchard analysis the apparent Kd (1–1.36 nmol/l) for the high affinity binding sites of the type I receptor is similar in all three preparations. Total binding capacity in ovine placental membranes is, however, 4 times lower. The affinity for the type II receptor is lower than for type I, whereas total binding capacity is higher. Affinity cross-linking confirms the competition experiments, showing binding of IGF-I to typical type I and of IGF-II to type II receptors.

Download Full-text

Insulin-like growth factor I (IGF-I), IGF-II and type-I IGF receptor gene expression in the ovary of the laying hen

Reproduction ◽

10.1530/jrf.0.1060101 ◽

1996 ◽

Vol 106 (1) ◽

pp. 101-106 ◽

Cited By ~ 14

Author(s):

D. G. Armstrong ◽

C. O. Hogg

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Receptor Gene ◽

Type I ◽

Insulin Like Growth Factor ◽

Factor I ◽

Type I Igf Receptor ◽

Igf I ◽

Igf Receptor ◽

Receptor Gene Expression

Download Full-text

Insulin-Like Growth Factor-I (IGF-I) and IGF-II Hormonal Action in Cultured Rat Granulosa Cells: Mediation via Type I but not Type II IGF Receptors*

Endocrinology ◽

10.1210/endo-126-1-216 ◽

1990 ◽

Vol 126 (1) ◽

pp. 216-222 ◽

Cited By ~ 57

Author(s):

ELI Y. ADASHI ◽

CAROL E. RESNICK ◽

RON G. ROSENFELD

Keyword(s):

Growth Factor ◽

Granulosa Cells ◽

Type I ◽

Insulin Like Growth Factor ◽

Type Ii ◽

Factor I ◽

Igf Receptors ◽

Igf I ◽

Hormonal Action ◽

Growth Factor I

Download Full-text

Growth hormone (GH) modulates insulin-like growth factor I (IGF-I) and type I IGF receptor mRNA levels in the ovary of prepubertal GH-deficient rats

Acta Endocrinologica ◽

10.1530/eje.0.1320497 ◽

1995 ◽

Vol 132 (4) ◽

pp. 497-501 ◽

Cited By ~ 4

Author(s):

Saul Malozowski ◽

Toni G Parmer ◽

Sabina Trojan ◽

George R Merriam ◽

Geula Gibori ◽

...

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Type I ◽

Mrna Levels ◽

Insulin Like Growth Factor ◽

Factor I ◽

Receptor Mrna ◽

Type I Igf Receptor ◽

Igf I ◽

Igf Receptor

Malozowski S, Parmer TG, Trojan S, Merriam GR, Gibori G, Roberts Jr CT, LeRoith D, Werner H, Zilberstein M. Growth hormone (GH) modulates insulin-like growth factor I (IGF-I) and type I IGF receptor mRNA levels in the ovary of prepubertal GH-deficient rats. Eur J Endocrinol 1995;132:497–501. ISSN 0804–4643 In order to explore the potential role of growth hormone (GH) in modulating insulin-like growth factor I (IGF-I) gene expression in the prepubertal rat ovary, female rats were rendered GH deficient by neonatal administration of monosodium glutamate (MSG). One group of rats received vehicle and served as the control. At 21 days of age, MSG-treated rats received either GH or vehicle for 2 weeks. On days 21, 24, 28 and 31 animals were weighed and subsets were sacrificed for liver RNA extraction. The remaining animals were sacrificed at day 35 when livers and ovaries were collected, and serum was obtained for GH determinations. The IGF-I mRNA levels were estimated by Northern blots and corroborated further by slot-blot analysis. The MSG-treated rats had lower body weights (p < 0.01) and GH levels (p < 0.05) than controls. Growth hormone replacement significantly accelerated the weight gain of MSG-treated rats. At day 24 and thereafter, three RNA IGF-I species (7.5, 1.8 and 0.8–1.2 kB) were seen in the liver. In the ovary, at age 35 days, two major IGF-I mRNA species (7.5 and 0.8–1.2kb) were seen. The MSG treatment consistently reduced the levels of both IGF-I mRNA species in the ovary. Growth hormone administration partially restored their expression, both in the liver and in the ovary. In addition, ovarian type I IGF receptor mRNA levels were increased in the MSG-treated rats when compared to controls. This trend was reversed by GH replacement. In summary, we have found that in prepubertal female rats rendered GH deficient with MSG, ovarian IGF-I gene expression is reduced while type I IGF receptor mRNA levels are increased. These findings are reversed with GH replacement. These results suggest a physiological role for GH in modulating IGF-I and type I IGF receptor genes in the ovary. Saul Malozowski, FDA, HFD-510, Rockville, MD 20897, USA

Download Full-text

The C Region of Human Insulin-like Growth Factor (IGF) I Is Required for High Affinity Binding to the Type 1 IGF Receptor

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)60418-1 ◽

1989 ◽

Vol 264 (19) ◽

pp. 11004-11008 ◽

Cited By ~ 3

Author(s):

M L Bayne ◽

J Applebaum ◽

D Underwood ◽

G G Chicchi ◽

B G Green ◽

...

Keyword(s):

Growth Factor ◽

Human Insulin ◽

Affinity Binding ◽

Insulin Like Growth Factor ◽

High Affinity Binding ◽

High Affinity ◽

Igf I ◽

Igf Receptor

Download Full-text

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

Journal of Endocrinology ◽

10.1677/joe.0.1200245 ◽

1989 ◽

Vol 120 (2) ◽

pp. 245-249 ◽

Cited By ~ 21

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

Download Full-text

Cellular Pattern of Insulin-Like Growth Factor-I (IGF-I) and Type I IGF Receptor Gene Expression in Early Organogenesis: Comparison with IGF-II Gene Expression

Molecular Endocrinology ◽

10.1210/mend-4-9-1386 ◽

1990 ◽

Vol 4 (9) ◽

pp. 1386-1398 ◽

Cited By ~ 224

Author(s):

Carolyn A. Bondy ◽

Haim Werner ◽

Charles T. Roberts ◽

Derek LeRoith

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Receptor Gene ◽

Type I ◽

Factor I ◽

Type I Igf Receptor ◽

Igf I ◽

Early Organogenesis ◽

Igf Receptor ◽

Receptor Gene Expression

Download Full-text

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

Biochemical Journal ◽

10.1042/bj2900419 ◽

1993 ◽

Vol 290 (2) ◽

pp. 419-426 ◽

Cited By ~ 178

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.

Download Full-text