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Gene Review

Igfbp3  -  insulin-like growth factor binding protein 3

Rattus norvegicus

Synonyms: IBP-3, IGF-binding protein 3, IGFBP-3, Igfbp-3, Insulin-like growth factor-binding protein 3
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Disease relevance of Igfbp3

  • Binding of (125)I-IGFBP-3 to platelet membranes was inhibited in a dose-dependent manner by recombinant Escherichia coli IGFBP-3 [1].
  • CONCLUSION: Cirrhosis is accompanied by an altered spatial expression of IGFBP-3 in liver tissue, which is characterized by decreased levels of IGFBP-3 mRNA in KC and SEC, but elevated IGFBP-3 expression in myofibroblast-like cells and inflammatory infiltrate [2].
  • The uterotrophic toxicity of chronic estradiol or tamoxifen treatment may be causally related to both the inhibition of uterine IGFBP-3 expression and the stimulation of uterine IGF-I expression by these compounds [3].
  • Treatment of rats with 1, 1.5, and 2 mg of ICI/kg body weight/week resulted in a 2-, 7-, and 8-fold increase in IGFBP-3 transcripts [4].
  • Impaired blockade of insulin-like growth factor I (IGF-I)-induced hypoglycemia by IGF binding protein-3 analog with reduced ternary complex-forming ability [5].

High impact information on Igfbp3

  • Angiotensin II markedly reduced plasma IGF I levels (56 and 41% decrease at 1 and 2 wk, respectively) and IGF binding protein-3 levels, and increased IGF binding protein-2 levels, a pattern suggestive of dietary restriction [6].
  • We hypothesized that levels of both hormones, their dominant BPs and liver IGF-I mRNA would fall, and that part of the mechanism for decreasing serum IGF-I would be enhanced IGFBP-3 protease activity [7].
  • The 0.02% dose of 2-DG had no effect on circulating levels of glucose, insulin, insulin-like growth factor-I, IGF binding protein-3, leptin, or body weight gain [8].
  • However, des(1-3)IGF-I, which weakly binds IGF binding protein-3 (IGFBP-3), induced IGF-IR phosphorylation [9].
  • At neutral pH, no IGFBP proteolysis was observed in conditioned media of early cultured and culture-activated HSCs, whereas at acidic pH, protease activities against IGFBP-3 and -4 were detectable [10].

Chemical compound and disease context of Igfbp3


Biological context of Igfbp3

  • Igfbp3 gene expression also was elevated in proliferating smooth muscle cells (SMCs) and was highest at the time of transition between proliferative and synthetic phases (Days 12-15) [15].
  • Because one of the functions of IGFBPs is to modulate IGF-I action on muscle size and phenotype, it is hypothesized that IGFBP-3 and -5 proteins may have potential modulatory roles in type I fiber-dominated muscles, aging, and regrowth from atrophy [16].
  • A weak signal was detected on estrus morning (E0200 h, E1000 h), but high levels of IGFBP-3 mRNA were observed in the stroma cells on Day 12 of pregnancy [17].
  • IGFBP-3 mRNA was not detectable at GD-20 but became detectable beginning at PND-5, and the signal intensity appeared to increase during stromal and muscle development [18].
  • Because the IGF and IGFBP-3 system plays an important role in prostate epithelial cell proliferation, apoptosis and tumour progression, the inhibitory effects of finasteride and ICI on IGF system may contribute to their anti-proliferative activity [19].

Anatomical context of Igfbp3


Associations of Igfbp3 with chemical compounds


Physical interactions of Igfbp3


Regulatory relationships of Igfbp3


Other interactions of Igfbp3


Analytical, diagnostic and therapeutic context of Igfbp3


  1. Characterisation of insulin-like growth factor-binding protein-3 binding to a novel receptor on human platelet membranes. Taylor, V.L., Spencer, E.M. J. Endocrinol. (2001) [Pubmed]
  2. Expression of insulin-like growth factor-I and insulin-like growth factor binding proteins during thioacetamide-induced liver cirrhosis in rats. Novosyadlyy, R., Dargel, R., Scharf, J.G. Growth Horm. IGF Res. (2005) [Pubmed]
  3. Uterotrophic actions of estradiol and tamoxifen are associated with inhibition of uterine insulin-like growth factor binding protein 3 gene expression. Huynh, H., Pollak, M. Cancer Res. (1994) [Pubmed]
  4. Inhibition of insulin-like growth factor signaling pathways in mammary gland by pure antiestrogen ICI 182,780. Chan, T.W., Pollak, M., Huynh, H. Clin. Cancer Res. (2001) [Pubmed]
  5. Impaired blockade of insulin-like growth factor I (IGF-I)-induced hypoglycemia by IGF binding protein-3 analog with reduced ternary complex-forming ability. Firth, S.M., McDougall, F., McLachlan, A.J., Baxter, R.C. Endocrinology (2002) [Pubmed]
  6. Angiotensin II causes weight loss and decreases circulating insulin-like growth factor I in rats through a pressor-independent mechanism. Brink, M., Wellen, J., Delafontaine, P. J. Clin. Invest. (1996) [Pubmed]
  7. Adaptation of the growth hormone and insulin-like growth factor-I axis to chronic and severe calorie or protein malnutrition. Oster, M.H., Fielder, P.J., Levin, N., Cronin, M.J. J. Clin. Invest. (1995) [Pubmed]
  8. 2-Deoxyglucose as an energy restriction mimetic agent: effects on mammary carcinogenesis and on mammary tumor cell growth in vitro. Zhu, Z., Jiang, W., McGinley, J.N., Thompson, H.J. Cancer Res. (2005) [Pubmed]
  9. Epidermal growth factor-induced activation of the insulin-like growth factor I receptor in rat hepatocytes. Hallak, H., Moehren, G., Tang, J., Kaou, M., Addas, M., Hoek, J.B., Rubin, R. Hepatology (2002) [Pubmed]
  10. Characterization of the IGF axis components in isolated rat hepatic stellate cells. Scharf, J.G., Knittel, T., Dombrowski, F., Müller, L., Saile, B., Braulke, T., Hartmann, H., Ramadori, G. Hepatology (1998) [Pubmed]
  11. Estradiol and triiodothyronine increase production of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) by GH4C1 rat pituitary tumor cells. Gilchrist, C.A., Park, J.H., MacDonald, R.G., Shull, J.D. Mol. Cell. Endocrinol. (1995) [Pubmed]
  12. Differential mRNA expression of insulin-like growth factor system during renal injury and hypertrophy. Hise, M.K., Li, L., Mantzouris, N., Rohan, R.M. Am. J. Physiol. (1995) [Pubmed]
  13. Inhibition of matrix metalloproteinases prevents cardiac hypertrophy induced by beta-adrenergic stimulation in rats. Miura, S., Ohno, I., Suzuki, J., Suzuki, K., Okada, S., Okuyama, A., Nawata, J., Ikeda, J., Shirato, K. J. Cardiovasc. Pharmacol. (2003) [Pubmed]
  14. Heparin inhibition of insulin-like growth factor-binding protein-3 binding to human fibroblasts and rat glioma cells: role of heparan sulfate proteoglycans. Yang, Y.W., Yanagishita, M., Rechler, M.M. Endocrinology (1996) [Pubmed]
  15. Insulin-like Growth Factors and Their Binding Proteins Define Specific Phases of Myometrial Differentiation During Pregnancy in the Rat. Shynlova, O., Tsui, P., Dorogin, A., Langille, B.L., Lye, S.J. Biol. Reprod. (2007) [Pubmed]
  16. Skeletal muscle IGF-binding protein-3 and -5 expressions are age, muscle, and load dependent. Spangenburg, E.E., Abraha, T., Childs, T.E., Pattison, J.S., Booth, F.W. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  17. Insulin-like growth factor binding proteins show distinct patterns of expression in the rat uterus. Girvigian, M.R., Nakatani, A., Ling, N., Shimasaki, S., Erickson, G.F. Biol. Reprod. (1994) [Pubmed]
  18. Tissue-specific expression of messenger ribonucleic acids for insulin-like growth factors and insulin-like growth factor-binding proteins during perinatal development of the rat uterus. Gu, Y., Branham, W.S., Sheehan, D.M., Webb, P.J., Moland, C.L., Streck, R.D. Biol. Reprod. (1999) [Pubmed]
  19. Co-administration of finasteride and the pure anti-oestrogen ICI 182,780 act synergistically in modulating the IGF system in rat prostate. Huynh, H., Alpert, L., Alaoui-Jamali, M.A., Ng, C.Y., Chan, T.W. J. Endocrinol. (2001) [Pubmed]
  20. Insulin-like growth factor (IGF)-I stimulates cell proliferation and induces IGF binding protein (IGFBP)-3 and IGFBP-5 gene expression in cultured growth plate chondrocytes via distinct signaling pathways. Kiepe, D., Ciarmatori, S., Hoeflich, A., Wolf, E., Tönshoff, B. Endocrinology (2005) [Pubmed]
  21. Octreotide prevents the early increase in renal insulin-like growth factor binding protein 1 in streptozotocin diabetic rats. Raz, I., Rubinger, D., Popovtzer, M., Grønbaek, H., Weiss, O., Flyvbjerg, A. Diabetes (1998) [Pubmed]
  22. Corticosterone regulation of insulin-like growth factor I, IGF-binding proteins, and growth in streptozotocin-induced diabetic rats. Rodgers, B.D., Strack, A.M., Dallman, M.F., Hwa, L., Nicoll, C.S. Diabetes (1995) [Pubmed]
  23. Increased plasma levels of growth hormone, insulin-like growth factor (IGF)-I and IGF-binding protein 3 in pregnant rats with exercise. Turgut, S., Kaptanoğlu, B., Emmungil, G., Turgut, G. Tohoku J. Exp. Med. (2006) [Pubmed]
  24. Growth hormone action on proliferation and differentiation of cerebral cortical cells from fetal rat. Ajo, R., Cacicedo, L., Navarro, C., Sánchez-Franco, F. Endocrinology (2003) [Pubmed]
  25. Growth hormone and parathyroid hormone stimulate IGFBP-3 in rat osteoblasts. Schmid, C., Schläpfer, I., Peter, M., Böni-Schnetzler, M., Schwander, J., Zapf, J., Froesch, E.R. Am. J. Physiol. (1994) [Pubmed]
  26. Regulation by glucocorticoids of cell differentiation and insulin-like growth factor binding protein production in cultured fetal rat nasal chondrocytes. Nadra, R., Menuelle, P., Chevallier, S., Berdal, A. J. Cell. Biochem. (2003) [Pubmed]
  27. Insulin-like growth factor binding protein expression in the hypothyroid rat is age dependent. Näntö-Salonen, K., Rosenfeld, R.G. Endocrinology (1992) [Pubmed]
  28. Signaling cross-talk between IGF-binding protein-3 and transforming growth factor-(beta) in mesenchymal chondroprogenitor cell growth. O'Rear, L., Longobardi, L., Torello, M., Law, B.K., Moses, H.L., Chiarelli, F., Spagnoli, A. J. Mol. Endocrinol. (2005) [Pubmed]
  29. Expression and insulin-like growth factor-dependent proteolysis of insulin-like growth factor-binding protein-4 are regulated by cell confluence in vascular smooth muscle cells. Kamyar, A., Pirola, C.J., Wang, H.M., Sharifi, B., Mohan, S., Forrester, J.S., Fagin, J.A. Circ. Res. (1994) [Pubmed]
  30. Reduction of ventral prostate weight by finasteride is associated with suppression of insulin-like growth factor I (IGF-I) and IGF-I receptor genes and with an increase in IGF binding protein 3. Huynh, H., Seyam, R.M., Brock, G.B. Cancer Res. (1998) [Pubmed]
  31. Regulation of insulin-like growth factor-binding proteins in rats with insulin-dependent diabetes mellitus. Rodgers, B.D., Bautista, R.M., Nicoll, C.S. Proc. Soc. Exp. Biol. Med. (1995) [Pubmed]
  32. Hormonal regulation of insulin-like growth factor II and insulin-like growth factor binding protein expression by breast cancer cells in vivo: evidence for stromal epithelial interactions. Manni, A., Badger, B., Wei, L., Zaenglein, A., Grove, R., Khin, S., Heitjan, D., Shimasaki, S., Ling, N. Cancer Res. (1994) [Pubmed]
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