Abstract
Insulin-like growth factor-I (IGF-I) is a pleiotrophic polypeptide which appears to have roles both as a circulating endocrine hormone and as a locally synthesized paracrine or autocrine tissue factor. IGF-I plays a major role in regulating the growth of cells in vivo and in vitro and initiates metabolic and mitogenic processes in a wide variety of cell types by binding to specific type I receptors in the plasma membrane. In this study, we report the distribution of IGF-I receptors in odontogenic cells at the ultrastructural level using the high resolution protein A-gold technique. In the pre-secretory stage, very little gold label was visible over the ameloblasts and odontoblasts. During the secretory stage the label was mostly seen in association with the cell membranes and endoplasmic reticulum of the ameloblasts. Lysosome-like elements in the post-secretory stage were labelled as well as multivesicular dense bodies. Very little labelling was encountered in the ameloblasts in the transitional stage, where apoptotic bodies were clearly visible. The maturation stage also exhibited labelling of the secretory-like granules in the distal surface. The presence of gold particles over the plasma membrane is an indication that IGF-I receptor is a membrane-bound receptor. Furthermore, the intracellular distribution of the label over the endoplasmic reticulum supports the local synthesis of the IGF-I receptor. The absence of labelling over the transitional ameloblasts suggests that the transitional stage may require the non-expression of IGF-I as a prerequiste or even a trigger for apoptosis.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Daughaday WH, Rotwein P. Insulin like growth factor I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocr Rev 1989; 10: 68–91.
Froesch ER, Schmid C, Schwander J, Zapf JA. Actions of insulin-like growth factors. Annu Rev Physiol 1985; 47: 443–467.
Steele-Perkins G, Turner J, Edman JC, et al. Expression and characterization of a functional human insulin-like growth factor I receptor. J Biol Chem 1988; 263: 11486–11492.
Czech MP. Signal transmission by the insulin-like growth factors. Cell 1989; 59: 235–238.
Rechler MM, Nissley SP. Insulin-like growth factors. In: Sporn MB, Roberts AB, eds. Peptide Growth Factors and Their Receptors I. New York, NY (USA): Springer-Verlag, 1990: 263–368.
LeRoith D, Roberts CT Jr. Insulin-like growth factor I (IGF-I): A molecular basis for endocrine versus local action? Mol Cell Endocrinol 1991; 77: C57–C61.
Warshawsky H, Smith CE. Morphological classification of rat incisor ameloblasts. Anat Rec 1974; 179: 423–446.
Sasaki T. Cell biology of tooth enamel formation. Functional electron microscopic monographs. Karger, Basel: Monographs in Oral Science, 1990: Vol. 14.
Joseph BK, Savage NW, Young WG, Gupta GS, Breier BH, Waters MJ. Expression and regulation of insulin-like growth factor-I in the rat incisor. Growth Factors 1993; 8: 267–275.
Smith CE, Warshawsky H. Quantitative analysis of cell turnover in the enamel organ of the rat incisor. Evidence for ameloblast death immediately after enamel matrix secretion. Anat Rec 1977; 187: 63–98.
Rubin R, Basera R. Insulin-like growth factor-I receptor: its role in cell proliferation, apoptosis and tumourgenicity. Lab Invest 1995; 73: 311–324.
Collins MK, Perkins GR, Rodriguez-Tarduchy-G, Nieto-MA, Lopez-Rivas-A. Growth factors as survival factors: regulation of apoptosis. Bioessays 1994; 16(2):133–138.
Joseph BK, Savage NW, Young WG, Waters MJ. Insulin-like growth factor-I receptor in the cell biology of the ameloblast: an immunohistochemical study. Epi Cell Biol 1994a; 3(2): 47–53.
Joseph BK, Gobé GC, Savage NW, Young WG. Expression and localization of sulphated glycoprotein-2 mRNA in the rat incisor tooth ameloblasts: relationships with apoptosis. Int J Exp Path 1994b; 75: 313–320.
Nanci A, Mckee MD, Smith CE. Immunolocalization of enamel proteins during amelogenesis in the cat. Anat Rec 1992; 233: 335–349.
Rosenzweig SA, Zetterstrom C, Benjamin A. Identification of retinal insulin receptors using site-specific antibodies to a carboxyl-terminal peptide of the human insulin receptor α-subunit. J Biol Chem 1990; 265: 18030–18034.
Lee PDK, Rosenfield RG, Hintz RL, Smith SD. Characterization of insulin, insulin like growth factors I and II and growth hormone receptors on human leukemic lymphoblasts. J Clin Endocrinol Metab 1986; 62: 28–34.
Pepe MG, Ginzton NH, Lee PDK, Hintz RL, Greenberg PL. Receptor binding and mitogenic effects of insulin and insulin-like growth factors I and II for human myeloid leukemic cells. J Cell Physiol 1987; 133: 219–223.
Trippel SB, Chernausek SD, Van Wyk JJ, Moses AC, Mankin HJ. Demonstration of type I and type II somatomedin receptors on bovine growth plate chondrocytes. J Orthpaed Res 1988; 6: 817–822.
Aron DC, Rosenzweig JL, Abboud HE. Synthesis and binding of insulin-like growth factor I by human glomerular mesangial cells. J Clin Endocrinol Metab 1989; 68: 585–589.
Centrella M, McCarthy TL, Canalis E. Receptors for insulin-like growth factors I and II in osteoblast-enriched cultures from fetal rat bone. Endocrinol 1990; 126: 39–44.
Resnicoff M, Abraham D, Yutanawiboonchai W, et al. The insulin-like growth factor I receptor protects tumor cells from apoptosis in vivo. Cancer Res 1995; 55: 2463–2469.
Posner BI. Polypeptide Hormone Receptors. New York, NY (USA): Dekker, 1985.
Carpentier JL. The journey of the insulin receptor into the cell: from cellular biology to pathophysiology. Histochem 1993; 100: 169–184.
Posner BI, Bergeron JJ, Josefsberg Z, et al. Polypeptide hormones intracellular receptor and internalization. Rec Prog Horm Res 1981; 37: 539–582.
Schalch DS, Sessions CM, Farley AC, Masakawa A, Emler CA, Dills DG. Interaction of insulin-like growth factor I/somatomedin-C with cultured rat chondrocytes: receptor binding and internalization. Endocrinol 1986; 118: 1590.
Bhaumick B, Bala RM. Receptors for insulin-like growth factors I and II in the developing mouse limb bud. Biochem Biophys Acta 1987; 927: 117–128.
Werner H, Woloschak M, Stannard B, Shen-Orr Z, Roberts CT Jr, LeRoith D. The insulin-like growth factor I receptor: Molecular biology, heterogeneity and regulation. In: LeRoith D, ed. Insulin-like Growth Factors: Molecular and Cellular Aspects. Boston, MA (USA): CRC Press, 1991: 17–47.
Kahn CR, Baird KL, Jarrett DB, Flier JS. Direct demonstration that receptor crosslinking or aggregation is important in insulin action. Proc Natl Acad Sci USA 1978; 75: 4209–4212.
Schlessinger J. Signal transduction by allosteric receptor oligomerization. Trends Biochem Sci 1988; 13: 443–446.
Kerr JFR, Wyllie AH, Currie AR. Apoptosis: a basic phenomenon with wide ranging implications in tissue kinetics. Br J Cancer 1972; 26: 293–297.
Wyllie AH, Kerr JF, Currie AR. Cell death: The significance of apoptosis. Int Rev Cytol 1980; 68: 251–253.
Kerr JFR, Harmon BV. Apoptosis: An historical perspective. In: Tomei LD, Cope FO, eds. Apoptosis: The Molecular Basis of Cell Death. Current Communications in Cell & Molecular Biology, 3. Cold Spring Harbor, NY (USA): Cold Spring Harbor Laboratory, 1991: 5–17.
Sandow BA, West NB, Norman RL, Brenner RM. Hormonal control of apoptosis in hamster uterine luminal epithelium. Am J Anat 1979; 156: 15–36.
Wyllie AH, Morris RG. Hormone-induced cell death. Purification and properties of thymocytes undergoing apoptosis after glucocorticoid treatment. Am J Pathol 1982; 109: 78–87.
Duke RC, Cohen JJ. IL-2 addiction: Withdrawal of growth factor activates a suicide program in dependent T cells. Lymphokine Res 1986; 5: 289–299.
Williams GT, Smith CA, Spooner E, Dexter TM, Taylor DR. Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis. Nature 1990; 343: 76–78.
Cohen JJ. Overview: Mechanisms of apoptosis. Immunol Today 1993; 14: 126–130.
Smith CE. Ameloblasts: Secretory and resorptive functions. J Dent Res 1979; 58B: 695–706.
Warshawsky H. Ultrastructural studies on amelogenesis. In: Butler WT, ed. The Chemistry and Biology of Mineralized Tissues. Birmingham, AL (USA): Ebsco Media, 1985: 33–45.
Moe H, Jessen H. Phagocytosis and elimination of amelocyte debris by stratum intermedium cells in the transitional zone of the enamel organ of the rat incisor. Z Zellforsch Mikrosk Anat 1972; 131: 63–75.
Smid JR, Monsour PA, Rousseau EM, Young WG. Cytochemical localization of dipeptidylpeptidase II activity in rat incisor tooth ameloblasts. Anat Record 1992; 233: 493–503.
Piacentini M, Autuori F, Dini L, et al. ‘Tissue’ transglutaminase is specifically expressed in neonatal rat liver cells undergoing apoptosis upon epidermal growth factor-stimulation. Cell Tissue Res 1991; 263: 227–235.
Alaoui S El, Mian S, Lawry J, Quash G, Griffin M. Cell cycle kinetics, tissue transglutaminase and programmed cell death (apoptosis). FEBS Lett 1992; 311: 174–178.
Knight RL, Hand D, Piacentini M, Griffin M. Characterization of the transglutaminase-mediated large molecular weight polymer from rat liver; its relationship to apoptosis. Eur J Cell Biol 1992; 60: 210–216.
Sugerman PB, Joseph BK, Savage NW. The role of oncogenes, tumour suppressor genes and growth factors in oral squamous cell carcinoma: a case of apoptosis versus proliferation. Oral Diseases 1995; 1: 172–188.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Joseph, B.K., Savage, N.W., Harbrow, D.J. et al. Non-expression of insulin-like growth factor-I receptor is associated with apoptosis: an ultrastructural study on rat ameloblasts. Apoptosis 2, 471–477 (1997). https://doi.org/10.1023/A:1026474128296
Issue Date:
DOI: https://doi.org/10.1023/A:1026474128296