Endocrinology, Vol 125, 766-772, Copyright © 1989 by Endocrine Society

ARTICLES

Insulin-like growth factor I (IGF-I)-binding protein complex is a better mitogen than free IGF-I

WF Blum, EW Jenne, F Reppin, K Kietzmann, MB Ranke and JR Bierich
University Children's Hospital, Tubingen, West Germany.

The insulin-like growth factors (IGF)-I and -II are bound to specific carrier proteins in the circulation. For investigation of their physiological role, the acid-stable subunit of the major binding protein (SmBP) was isolated from human plasma Cohn fraction IV. Its effect on the mitogenic activity of IGF-I was studied with baby hamster kidney fibroblasts (BHK-21) and human skin fibroblasts. While free IGF- I had no effect on thymidine incorporation into DNA with BHK-21 cells and only a moderate effect with human fibroblasts under standard conditions, DNA synthesis was significantly enhanced with both cell lines if IGF-I was complexed with SmBP before the experiment. The enhancement was optimal at an approximately equimolar ratio of both peptides. In contrast to experiments in which large concentrations of IGF-I were added at the beginning, repeated addition of small quantities of free IGF-I at hourly intervals clearly stimulated DNA synthesis in BHK-21 cells. Binding studies with radiolabeled SmBP revealed no evidence for direct interaction with either cell line. It is concluded that SmBP acts as a reservoir, releasing continuously low amounts of IGF-I and thereby creating a steady state situation of receptor occupancy, which appears to be a better mitogenic stimulus than temporary large concentrations of IGF-I.

This article has been cited by other articles:

				S Llewellyn, R Fitzpatrick, D A Kenny, J J Murphy, R J Scaramuzzi, and D C Wathes Effect of negative energy balance on the insulin-like growth factor system in pre-recruitment ovarian follicles of post partum dairy cows Reproduction, March 1, 2007; 133(3): 627 - 639. [Abstract] [Full Text] [PDF]

				J. V. Silha, Y. Gui, S. Mishra, A. Leckstrom, P. Cohen, and L. J. Murphy Overexpression of Gly56/Gly80/Gly81-Mutant Insulin-Like Growth Factor-Binding Protein-3 in Transgenic Mice Endocrinology, March 1, 2005; 146(3): 1523 - 1531. [Abstract] [Full Text] [PDF]

				M. G. Slomiany and S. A. Rosenzweig Autocrine effects of IGF-I-induced VEGF and IGFBP-3 secretion in retinal pigment epithelial cell line ARPE-19 Am J Physiol Cell Physiol, September 1, 2004; 287(3): C746 - C753. [Abstract] [Full Text] [PDF]

				M. G. Slomiany and S. A. Rosenzweig IGF-1-Induced VEGF and IGFBP-3 Secretion Correlates with Increased HIF-1{alpha} Expression and Activity in Retinal Pigment Epithelial Cell Line D407 Invest. Ophthalmol. Vis. Sci., August 1, 2004; 45(8): 2838 - 2847. [Abstract] [Full Text] [PDF]

				J. H. Lai, D. Vesprini, W. Zhang, M. J. Yaffe, M. Pollak, and S. A. Narod A Polymorphic Locus in the Promoter Region of the IGFBP3 Gene Is Related to Mammographic Breast Density Cancer Epidemiol. Biomarkers Prev., April 1, 2004; 13(4): 573 - 582. [Abstract] [Full Text] [PDF]

				C. Palermo, P. Manduca, E. Gazzerro, L. Foppiani, D. Segat, and A. Barreca Potentiating role of IGFBP-2 on IGF-II-stimulated alkaline phosphatase activity in differentiating osteoblasts Am J Physiol Endocrinol Metab, April 1, 2004; 286(4): E648 - E657. [Abstract] [Full Text] [PDF]

				L. Longobardi, M. Torello, C. Buckway, L. O'Rear, W. A. Horton, V. Hwa, C. T. Roberts Jr., F. Chiarelli, R. G. Rosenfeld, and A. Spagnoli A Novel Insulin-Like Growth Factor (IGF)-Independent Role for IGF Binding Protein-3 in Mesenchymal Chondroprogenitor Cell Apoptosis Endocrinology, May 1, 2003; 144(5): 1695 - 1702. [Abstract] [Full Text] [PDF]

				J. V. Silha and L. J. Murphy Minireview: Insights from Insulin-Like Growth Factor Binding Protein Transgenic Mice Endocrinology, October 1, 2002; 143(10): 3711 - 3714. [Abstract] [Full Text] [PDF]

				J. V. Silha, Y. Gui, T. Modric, A. Suwanichkul, S. K. Durham, D. R. Powell, and L. J. Murphy Overexpression of the Acid-Labile Subunit of the IGF Ternary Complex in Transgenic Mice Endocrinology, October 1, 2001; 142(10): 4305 - 4313. [Abstract] [Full Text] [PDF]

				G. E. Walker, E. M. Wilson, D. Powell, and Y. Oh Butyrate, a Histone Deacetylase Inhibitor, Activates the Human IGF Binding Protein-3 Promoter in Breast Cancer Cells: Molecular Mechanism Involves an Sp1/Sp3 Multiprotein Complex Endocrinology, September 1, 2001; 142(9): 3817 - 3827. [Abstract] [Full Text] [PDF]

				T. Modric, J. V. Silha, Z. Shi, Y. Gui, A. Suwanichkul, S. K. Durham, D. R. Powell, and L. J. Murphy Phenotypic Manifestations of Insulin-Like Growth Factor-Binding Protein-3 Overexpression in Transgenic Mice Endocrinology, May 1, 2001; 142(5): 1958 - 1967. [Abstract] [Full Text]

				N. Anim-Nyame, F.A. Hills, S.R. Sooranna, P.J. Steer, and M.R. Johnson A longitudinal study of maternal plasma insulin-like growth factor binding protein-1 concentrations during normal pregnancy and pregnancies complicated by pre-eclampsia Hum. Reprod., October 1, 2000; 15(10): 2215 - 2219. [Abstract] [Full Text] [PDF]

				C. A. Conover, L. K. Bale, S. K. Durham, and D. R. Powell Insulin-Like Growth Factor (IGF) Binding Protein-3 Potentiation of IGF Action Is Mediated through the Phosphatidylinositol-3-Kinase Pathway and Is Associated with Alteration in Protein Kinase B/AKT Sensitivity Endocrinology, September 1, 2000; 141(9): 3098 - 3103. [Abstract] [Full Text] [PDF]

				R. C. Baxter Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities Am J Physiol Endocrinol Metab, June 1, 2000; 278(6): E967 - E976. [Abstract] [Full Text] [PDF]

				M. E. Wilson Insulin-Like Growth Factor I (IGF-I) Replacement during Growth Hormone Receptor Antagonism Normalizes Serum IGF-Binding Protein-3 and Markers of Bone Formation in Ovariectomized Rhesus Monkeys J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1557 - 1562. [Abstract] [Full Text]

				A. Anwar, A. A. Zahid, L. Phillips, and P. Delafontaine Insulin-Like Growth Factor Binding Protein-4 Expression Is Decreased by Angiotensin II and Thrombin in Rat Aortic Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., February 1, 2000; 20(2): 370 - 376. [Abstract] [Full Text] [PDF]

				C. Kristensen, F. C. Wiberg, and A. S. Andersen Specificity of Insulin and Insulin-like Growth Factor I Receptors Investigated using Chimeric Mini-Receptors. ROLE OF C-TERMINAL OF RECEPTOR alpha SUBUNIT J. Biol. Chem., December 24, 1999; 274(52): 37351 - 37356. [Abstract] [Full Text] [PDF]

				G. N. Fuller, C. H. Rhee, K. R. Hess, L. S. Caskey, R. Wang, J. M. Bruner, W. K. A. Yung, and W. Zhang Reactivation of Insulin-like Growth Factor Binding Protein 2 Expression in Glioblastoma Multiforme: A Revelation by Parallel Gene Expression Profiling Cancer Res., September 1, 1999; 59(17): 4228 - 4232. [Abstract] [Full Text] [PDF]

				H. Hirano, M. B. S. Lopes, E. R. Laws Jr., T. Asakura, M. Goto, J. E. Carpenter, L. R. Karns, and S. R. VandenBerg Insulin-like growth factor-1 content and pattern of expression correlates with histopathologic grade in diffusely infiltrating astrocytomas Neuro-oncol, April 1, 1999; 1(2): 109 - 119. [Abstract] [PDF]

				Y. Yamanaka, J. L. Fowlkes, E. M. Wilson, R. G. Rosenfeld, and Y. Oh Characterization of Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3) Binding to Human Breast Cancer Cells: Kinetics of IGFBP-3 Binding and Identification of Receptor Binding Domain on the IGFBP-3 Molecule Endocrinology, March 1, 1999; 140(3): 1319 - 1328. [Abstract] [Full Text]

				C. Agarwal, A. Lambert, R. A.S. Chandraratna, E. A. Rorke, and R. L. Eckert Vitamin D Regulates Human Ectocervical Epithelial Cell Proliferation and Insulin-Like Growth Factor-Binding Protein-3 Level Biol Reprod, March 1, 1999; 60(3): 567 - 572. [Abstract] [Full Text]

				S. L. Bradshaw, A. J. D’Ercole, and V. K. M. Han Overexpression of Insulin-Like Growth Factor-Binding Protein-2 in C6 Glioma Cells Results in Conditional Alteration of Cellular Growth Endocrinology, February 1, 1999; 140(2): 575 - 584. [Abstract] [Full Text]

				M. E. Wilson Effects of Estradiol and Exogenous Insulin-Like Growth Factor I (IGF-I) on the IGF-I Axis during Growth Hormone Inhibition and Antagonism J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 4013 - 4021. [Abstract] [Full Text]

				A. Nishimura, M. Fujimoto, S. Oguchi, R. D. Fusunyan, R. P. MacDermott, and I. R. Sanderson Short-chain fatty acids regulate IGF-binding protein secretion by intestinal epithelial cells Am J Physiol Endocrinol Metab, July 1, 1998; 275(1): E55 - E63. [Abstract] [Full Text] [PDF]

				S. M. Twigg and R. C. Baxter Insulin-like Growth Factor (IGF)-binding Protein 5 Forms an Alternative Ternary Complex with IGFs and the Acid-labile Subunit J. Biol. Chem., March 13, 1998; 273(11): 6074 - 6079. [Abstract] [Full Text] [PDF]

				J. A. M. J. L. Janssen, R. P. Stolk, H. A. P. Pols, D. E. Grobbee, and S. W. J. Lamberts Serum Total IGF-I, Free IGF-I, and IGFBP-1 Levels in an Elderly Population : Relation to Cardiovascular Risk Factors and Disease Arterioscler. Thromb. Vasc. Biol., February 1, 1998; 18(2): 277 - 282. [Abstract] [Full Text] [PDF]

				S. Rajaram, D. J. Baylink, and S. Mohan Insulin-Like Growth Factor-Binding Proteins in Serum and Other Biological Fluids: Regulation and Functions Endocr. Rev., December 1, 1997; 18(6): 801 - 831. [Abstract] [Full Text]

				S. Manes, L. Kremer, J. P. Albar, C. Mark, R. Llopis, and C. Martinez-A Functional Epitope Mapping of Insulin-Like Growth Factor I (IGF-I) by Anti-IGF-I Monoclonal Antibodies Endocrinology, March 1, 1997; 138(3): 905 - 915. [Abstract] [Full Text] [PDF]

				B. C. Villafuerte, W. Zhao, A. C. Herington, R. Saffery, and L. S. Phillips Identification of an Insulin-responsive Element in the Rat Insulin-like Growth Factor-binding Protein-3 Gene J. Biol. Chem., February 21, 1997; 272(8): 5024 - 5030. [Abstract] [Full Text] [PDF]