Presence of insulinlike growth factor receptors and lack of insulin receptors on fetal bovine smooth muscle cells

In Vitro Cellular & Developmental Biology - Plant - Tập 24 - Trang 921-926 - 1988
Phillip D. K. Lee1, Raymond L. Hintz1, Ron G. Rosenfeld1, William E. Benitz1
1Department of Pediatrics, Stanford University, Stanford

Tóm tắt

Previous investigations have demonstrated specific receptors and associated mitogenic actions for insulin and insulinlike growth factors I and II (IGF-I and II) in postnatal bovine aortic smooth muscle. Using fetal tissue we have observed different patterns of binding and action for these peptides. Smooth muscle cells isolated from near-term fetal bovine aortae were studied in early passage. Specific receptors for both IGF-I and IGF-II were identified. Specific binding averaged 5.7%/2.5×105 cells for IGF-I, and 16.2% for IGF-II, and 0.3% for insulin. High affinity K d for both IGF receptors were nanomolar. IGF-II was fivefold less potent than IGF-I in displacing IGF-I binding. IGF-I showed no affinity for the IGF-II receptor. Insulin, at physiologic concentrations, was incapable of displacing either IGF-I or IGF-II binding. Cellular incorporation of [methyl-3H]thymidine was stimulated at the lowest dose of IGF-I tested, 0.5 ng/ml. IGF-II showed no effect up to 100 ng/ml, after which a sharp increase in incorporation was noted. Insulin had a similar effect only at concentrations >0.5 μg/ml, with a maximal response noted at 5 to 10 μg/ml. Our results indicate that fetal bovine aortic smooth muscle cells have an abundance of IGF receptors but lack specific insulin receptors. In addition, IGF-II binding levels are three times higher than for IGF-I. These results are consistent with observations in other species, in which a predominance of IGF over insulin receptors has been demonstrated in fetal tissue, and provide further evidence for a role for the IGFs in embryonic cellular metabolism.

Tài liệu tham khảo

Wilson, D. M.; Hintz, R. L. Inter-species comparison of somatomedin structure using immunological probes. J. Endocrinol. 95:59–64; 1982. Daughaday, W. H.; Kapadia, M.; Yanow, C. E., et al. Insulin-like growth factors I and II of nonmammalian sera. Gen. Comp. Endocrinol. 59:316–325; 1985. Roberts, C. T., Jr.; Lasky, S. R.; Lowe, W. L., Jr., et al. Molecular cloning of rat insulin-like growth factor I complementary deoxyribonucleic acid: differential messenger ribonucleic acid processing and regulation by growth hormone in extrahepatic tissues Mol. Endocrinol. 1:243–248; 1987. Dull, T. J.; Gray, A.; Hayflick, J. S., et al. Insulin-like growth factor II precursor gene organization in relation to insulin gene family. Nature 310:777–786; 1984. Rechler, M.; Nissley, S. P. The nature and regulation of the receptors for insulin-like growth factors. Annu. Rev. Physiol. 47:425–442; 1985. Gluckman, P. D.; Butler, J. H. Insulin-like growth factors in the fetus. In: Jones, C. T.; Nathanielsz, P. W., eds. The physiological development of the fetus and newborn. New York: Academic Press; 1985:21–25. Underwood, L. E.; D'Ercole, A. J. Insulin and insulin-like growth factors/somatomedins in fetal and neonatal development. Clin. Endocrinol. Metab. 13:69–89; 1984. Ross, R.; Klebanoff, S. J. The smooth muscle cell. 1. In vivo synthesis of connective tissue proteins. J. Cell. Biol. 50:159–171; 1971. Benitz, W. E.; Lessler, D. S.; Coulson, J. D., et al. Heparin inhibits proliferation of fetal vascular smooth muscle cells in the absence of platelet-derived growth factors. J. Cell. Physiol. 127:1–7; 1986. Schalch, D.; Reissman, D.; Emler, C., et al. Insulin-like growth factor I/somatomedin-C (IGF-I/SmC): comparison of natural, solid phase synthetic and recombinant DNA analog peptides in two radioligand assays. Endocrinology 115:2490–2492; 1984. Li, C. H.; Yamashiro, D.; Hammonds, R. G., Jr., et al. Synthetic insulin-like growth factor II. Biochem. Biophys. Res. Commun. 127:420–424; 1985. Enberg, G.; Carlquist, M.; Jornvall, H., et al. The characterization of somatomedin A, isolated by microcomputer-controlled chromatography, reveals an, apparent identity to insulin-like growth factor I. Eur. J. Biochem. 143:117–124; 1984. Hunter, W. M.; Greenwood, F. C. Preparation of iodine-131 labeled human growth hormone of high specific activity. Nature 194:495–496; 1962. Munson, P.; Rodbard D. LIGAND: a versatile computerized approach for characterization of ligand binding systems. Anal. Biochem. 107:220–239; 1980. Moses, A. C.; Nissley, S. P.; Short, P. A., et al. Increased levels of multiplication stimulating activity, an insulin-like growth factor, in fetal rat serum. Proc. Natl. Acad. Sci. USA 77:3649–3653; 1980. Adams, S. O.; Nissley, S. P.; Handwerger, S., et al. Developmental patterns of insulin-like growth factor-I and-II synthesis and regulation in rat fibroblasts. Nature 302:150–153; 1983. Daughaday, W. H.; Mariz, I. K.; Trivedi, B. A preferential binding site for insulin-like growth factor II in human and rat placental membranes. J. Clin. Endocrinol. Metab. 53:282–288; 1981. Adams, S. O.; Nissley, S. P.; Kasuga, M., et al. Receptors for insulin-like growth factors and growth effects of multiplication-stimulating activity (rat insulin-like growth factor II) in rat embryo fibroblasts. Endocrinology 112:971–978; 1983. Hill, D. J.; Crace, C. J.; Fowler, L., et al. Cultured fetal rat myoblasts release peptide growth factors which are immunologically and biologically similar to somatomedin. J. Cell. Physiol. 119:349–358; 1984. Hill, D. J.; Crace, C. J.; Nissley, S. P., et al. Fetal rat myoblasts release both rat somatomedin-C (SM-C)/insulin-like growth factor I (IGF-I) and multiplication-stimulating activity in vitro: partial characterization and biological activity of myoblast-derived SM-C/IGF-I. Endocrinology 117:2061–2072; 1985. Nagarajan, L.; Anderson, W. B.; Nissley, S. P., et al. Production of insulin-like growth factor-II (MSA) by endoderm-like cells derived from embryonal carcinoma cells: possible mediator of embryonic cell growth. J. Cell. Physiol. 124:199–206; 1985. Bassas, L.; de Pablo, F.; Lesniak, M. A., et al. Ontogeny of receptors for insulin-like peptides in chick embryo tissues: early dominance of insulin-like growth factor over insulin receptors in brain. Endocrinology 117:2321–2329; 1985. Hill, D. J.; Crace, C. J.; Strain, A. J., et al. Regulation of amino acid uptake and deoxyribonucleic acid synthesis in isolated human fetal fibroblasts and myoblasts: effect of human placental lactogen, somatomedin-C, multiplication-stimulating activity, and insulin. J. Clin. Endocrinol. Metab. 62:743–760; 1986. Gospodarowicz, D.; Hirabayashi, K.; Giguere, L., et al. Factors controlling the proliferative rate, final cell density, and life span of bovine vascular smooth muscle cells in culture. J. Cell. Biol. 89:568–578; 1981. Clemmons, D. R.; Van Wyk, J. J. Evidence for a functional role of endogenously produced somatomedinlike peptides in the regulation of DNA synthesis in cultured human fibroblasts and porcine smooth muscle cells. J. Clin. Invest. 75:1914–1918; 1985. King, G. L.; Buzney, S. M.; Kahn, C. R., et al. Differential responsiveness to insulin of endothelial and support cells from micro- and macrovessels. J. Clin. Invest. 71:974–979; 1983. King, G. L.; Goodman, A. D.; Buzney, S., et al. Receptors and growth-promoting effects of insulin and insulinlike growth factors on cells from bovine retinal capillaries and aorta. J. Clin. Invest. 75:1028–1036; 1985. Jialal, I.; Crettaz, M.; Hachiya, H. L., et al. Characterization of the receptors for insulin and the insulin-like growth factors on micro- and macrovascular tissues Endocrinology 117:1222–1229; 1985. Lee, P. D. K.; Hodges, D.; Hintz, R. L., et al. Identification of receptors for insulin-like growth factor II in two insulin-like growth factor II producing cell lines. Biochem. Biophys. Res. Commun. 134:595–600; 1986. Rosenfeld, R. G.; Conover, C. A.; Hodges, D., et al. Heterogeneity of insulin-like growth factor-I affinity for the insulin-like growth factor-II receptor: comparison of natural, synthetic and recombinant DNA-dervied insulin-like growth factor-I. Biochem. Biophys. Res. Commun. 143:199–205; 1987. Libby, P.; O'Brien, K. V. Culture of quiescent arterial smooth muscle cells in a defined serum-free medium. J. Cell. Physiol. 115:217–223; 1983. Banskota, N.; Zellner, K.; Taub, R., et al. Stimulation of mycgene expression through the IGF-I receptor: an early step in insulin and IGF's mitogenic effect on arterial smooth muscle cells. Clin. Res. 34:539; 1986. Shimizu, M.; Webster, C.; Morgan, D. O., et al. Insulin and insulinlike growth factor receptors and responses in cultured human muscle cells. Am. J. Physiol. 251:E611–615; 1986. Conover, C. A.; Misra, P.; Hintz, R. L., et al. Effect of an anti-insulin-like growth factor I receptor antibody on insulin-like growth factor II stimulation of DNA synthesis in human fibroblasts. Biochem. Biophys. Res. Commun. 139:501–508; 1986. Morgan, D. O.; Edman, J. C.; Standring, D. N., et al. Insulin-like growth factor II receptor as a multifunctional binding protein. Nature 329:301–307; 1987.