IGF1 (insulin-like growth factor 1), basic characteristics, biological effect, age and gender dependence

Czech version

Authors: R. Kučera; O. Topolčan; L. Pecen; V. Šimánek
Authors‘ workplace: Oddělení nukleární medicíny, Imunoanalytická laboratoř, FN a LF v Plzni, Univerzita Karlova v Praze
Published in: Klin. Biochem. Metab., 24, 2016, No. 1, p. 14-19

Overview

Signaling pathway of IGF1 (insulin-like growth factor 1) belongs to the most important growth pathways in the organism. This pathway has been studied for many years in connection with the growth and survival of cells and in recent years also in connection with the cancer development.

Over time, the step from IGF1 serum levels to the mapping of the occurrence of IGF1 in tissues was done, further, we observed that the effect is mediated by a specific receptor, which is located on the cell surface. Finally, we found location of genes which encoded IGF1, its binding protein and its receptor. The entire way of IGF1 in human body was described, from its synthesis, transport in serum and receptor binding. Also the individual components of cellular signaling pathways were identified starting IGF1 receptor till the individual effectors within the cell. These findings allow us to give an idea about the functioning of IGF1 and its role in the growth, differentiation and cell surviving. IGF1 depends on age and gender, which must be respected when reference ranges are established.

Keywords:
Insulin-like growth factors, binding proteins, receptors, age and gender dependence.

Sources

1. Ketha, H., Singh, R. J. Clinical assays for quantitation of insulin-like-growth-factor-1 (IGF1). Methods. 2015 Jun 15, 81, p. 93-8.

2. Dupont, J., LeRoith, D. Insulin and insulin-like growth factor I receptors: similarities and differences in signal transduction, Horm. Res., 55 Suppl. 2, p. 22-6.

3. Powell-Braxton, L., Hollingshead, P., Warburton, C., Dowd, M., Pitts-Meek, S., Dalton, D., Gillett, N., Ste-wart, T. A. IGF-I is required for normal embryonic growth in mice, Genes Dev., Dec. 1993, 7 (12B), p. 2609-17.

4. DeChiara, T. M., Efstratiadis, A., Robertson, E. J. A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting, Nature, 1990, 345 (6270), p. 78-80.

5. Bach, L. A. Endothelial cells and the IGF system. J. Mol. Endocrinol., 2015, Feb 54 (1), R1-13.

6. Nakae, J., Kido, Y., Accili, D. Distinct and overlapping functions of insulin and IGF-I receptors, Endocrine Rev., 2001, 22, p. 818-35.

7. Riedemann, J., Macaulay, V. M. IGFIR signaling and its inhibition, Endocrine Related Cancer, 2006, Suppl.1, p. 33-43.

8. Hishiya, A., Ito, M., Aburatani, H., Motoyama, N., Ikeda, K., Watanabe, K. Ataxia telangiectasia mutated (Atm) knockout mice as a model of osteopenia due to impaired bone formation. Bone, 2005 Oct. 37 (4), p. 497-503.

9. Renehan, A. G., Zwahlen, M., Minder, C., O’Dwyer, S. T., Shalet, S. M., Egger, M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: syste-matic review and meta-regression analysis. Lancet, 2004, 363, p. 1346-1353.

10. Bruchim, I., Sarfstein, R., Werner, H. The IGF Hormonal Network in Endometrial Cancer: Functions, Regulation, and Targeting Approaches. Front Endocrinol., 2014, May 19, 5, p. 76.

11. McCampbell, A. S., Broaddus, R. R., Loose, D. S., Davies, P. J. Overexpression of the insulin-like growth factor I receptor and activation of the AKT pathway in hyperplastic endometrium. Clin. Cancer. Res., 2006, Nov 1, 12 (21), p. 6373-8.

12. Monti, S., Proietti-Pannunzi, L., Sciarra, A., Lolli, F., Falasca, P., Poggi, M., Celi, F. S., Toscano, V. The IGF axis in prostate cancer. 2007, Curr. Pharm. Des., 13, p. 719-27. In: Samani, A. A., Yakar, S., LeRoith, D., Brodt, P. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr. Rev., 2007, 28, p. 20-47.

13. Vorwerk, P., Wex, H., Hohmann, B., Mohnike, K., Schmidt, U., Mittler, U. Expression of components of the IGF signalling system in childhood acute lymphoblastic leukaemia. Mol. Pathol. 2002.

14. Sutherland, B. W., Knoblaugh, S. E., Kaplan-Lefko, P. J., Wang, F., Holzenberger, M., Greenberg, N. M. Conditional deletion of insulin-like growth factor-I receptor in prostate epithelium. Cancer Res., 2008, May 1, 68 (9), p. 3495-504.

15. Mari, D. Role of the IGF/insulin system in longevity. Minerva Endocrinol., 2011, 36, p. 181-5.

16. Bartke, A., Brown-Borg, H. Life extension in the dwarf mouse. Curr. Top Dev. Biol., 2004, 63, p. 189-225.

17. Leite, D. B., Meirelles, R. M. Mandarim-de-Lacerda, C. A., Matos, H. J., Bernardo-Filho, M. Serum insulin-like growth factor-I adult reference values for an automated chemiluminescence immunoassay system. Afr. J Biotechnol. 2011, 10, p. 18027-33.

18. Friedrich, N., Alte, D., Völzke, H., Spilcke-Liss, E., Lüdemann, J., Lerch, M. M. et al. Reference ranges of serum IGF-1 and IGFBP-3 levels in a general adult population: Results of the Study of Health in Pomerania (SHIP). Growth Horm. IGF Res., 2008, 18, p. 228-37.

19. Sandhu, M. S., Dunger, D. B., Giovannucci, E. L. Insulin, insulin-like growth factor-I (IGF-I), IGF binding proteins, their biologic interactions, and colorectal cancer. J Natl. Cancer Inst., 2002, Jul 3, 94 (13), p. 972-80.

20. Alberti, C., Chevenne, D., Mercat, I., Josserand, E., Armoogum-Boizeau, P., Tichet, J., Léger, J. Serum concentrations of insulin-like growth factor (IGF)-1 and IGF binding protein-3 (IGFBP-3), IGF-1/IGFBP-3 ratio, and markers of bone turnover: reference values for French children and adolescents and z-score comparability with other references. Clin. Chem., 2011, Oct 57 (10), p. 1424-35.

21. Rosario, P. W. Normal values of serum IGF-1 in adults: results from a Brazilian population. Arq. Bras. Endocrinol. Metabol., 2010, 54 (5), p. 477-81.

22. Kucera, R., Topolcan, O., Pecen, L., Kinkorova, J., Svobodova, S., Windrichova, J., Fuchsova, R. Re-ference values of IGF1, IGFBP3 and IGF1/IGFBP3 ratio in adult population in the Czech Republic. Clin. Chim. Acta., 2015 Apr 15, p. 444:271.

23. Friedrich, N., Wolthers, O. D., Arafat, A. M., Emeny, R. T., Spranger, J., Roswall, J., Kratzsch, J., Grabe, H. J., Hübener, C., Pfeiffer, A. F., Döring, A., Bielohuby, M., Dahlgren, J., Frystyk, J., Wallaschofski, H., Bidlingmaier, M. Age- and sex-specific reference intervals across life span for insulin-like growth factor binding protein 3 (IGFBP-3) and the IGF-I to IGFBP-3 ratio measured by new automated chemiluminescence assays. J. Clin. Endocrinol. Metab., 2014, 99, p. 1675-86.

24. Guven, B., Can, M., Mungan, G., Acikgoz, S. Refe-rence values for serum levels of insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3) in the West Black Sea region of Turkey. Scand. J Clin. Lab. Invest., 2013, 73, p. 135-40.

25. Lin, C. M., Huang, Y. L., Lin, Z. Y. Influence of gender on serum growth hormone, insulin-like growth factor-I and its binding protein-3 during aging. Yonsei Med. J., 2009, 50, p. 407-13.

26. Wright, E. M., Royston, P. Simplified estimation of age-specific reference interval for skewed data. Stat. Med., 1997, 16, p. 2785-803.

27. Kucera, R., Cerna, M., Narsanska, A., Svobodova, S., Strakova, M., Vrzalova, J., Fuchsova, R., Treskova, I., Kydlicek, T., Treska, V., Pecen, L., Topolcan, O., Pazdiora, P. Growth factors and breast tumors, comparison of selected growth factors with traditional tumor markers. Anticancer Res., 2011, Dec 31(12), p. 4653-6.

Labels

Clinical biochemistry Nuclear medicine Nutritive therapist

Antibody structure and its reactivity.

Actualization of knowledge about the state of measurement of 25-hydroxyvitamin D in serum. A mini-review 2015 – 2016.

Influence of IGF1 (insulin-like growth factor 1) signaling pathway to the development of cancer diseases

The role of mitochondria in pathogenesis of Huntington´s disease

Criteria of analytical quality measurement in clinical biochemistry. Current international consensus and its implications for routine action of clinical laboratories.

Article was published in

Clinical Biochemistry and Metabolism

2016 Issue 1