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Gene Review

IGFBP3  -  insulin-like growth factor binding protein 3

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Disease relevance of IGFBP3


High impact information on IGFBP3


Biological context of IGFBP3

  • Expression patterns for certain genes (e.g., IGFBP3, HNF4A, GPAM) revealed adaptations commencing well ahead of parturition, suggesting they are regulated by factors other than periparturient hormonal environment [9].
  • Whereas cultured human fibroblasts may be suitable to study posttranscriptional regulation of IGFBP-3 availability, cultured bovine fibroblasts may provide a useful model system to probe the molecular mechanisms of IGFBP-3 gene expression and regulation by IGF-I [10].
  • Northern blotting indicated that endogenous IGFBP-3 mRNA, which was undetectable in wild-type (WT) MDBK cells, was expressed in MDBKpMONBP-3 cells while the IGFBP-3 transgene did not appear to be expressed [11].
  • The alterations in morphology and IGFBP-3 expression were irreversible, since MDBKpMONBP-3 cells failed to revert to the WT phenotype upon removal of MTX and dialyzed serum [11].
  • These results demonstrate that IGFBP-3 protein and RNA are expressed predominantly during early diestrus in the bovine CL [12].

Anatomical context of IGFBP3


Associations of IGFBP3 with chemical compounds


Physical interactions of IGFBP3


Regulatory relationships of IGFBP3


Other interactions of IGFBP3

  • In contrast to its effect in bovine fibroblasts, IGF-I had no significant effect on steady state levels of IGFBP-3 mRNA in cultured human fibroblasts [10].
  • We demonstrated that GH reduces mRNA and protein expression of IGFBP-5 in BMECs, but it does not affect the expression of IGFBP-3 [19].
  • Vascular endothelial growth factor inhibited IGFBP-3 mRNA (P < 0.01) and protein expression and increased IGFBP-5 mRNA (P < 0.001) and protein [18].
  • The amounts of IGFBP-3 in conditioned media were relatively low under basal conditions when analyzed by ligand blotting with 125I-IGF-II, but were increased dramatically relative to serum-free controls by exposure to IGF-I (100 ng/ml) or IGF-II (100 ng/ml) for 24 h [21].
  • In ligand blots IGFBP-3 and IGFBP-4 appeared as the most prominent species [22].

Analytical, diagnostic and therapeutic context of IGFBP3


  1. Insulin-like growth factor binding protein-2 mediates the inhibition of DNA synthesis by transforming growth factor-beta in mink lung epithelial cells. Dong, F., Wu, H.B., Hong, J., Rechler, M.M. J. Cell. Physiol. (2002) [Pubmed]
  2. Modulation of insulin-like growth factor (IGF) and IGF binding protein biosynthesis by hypoxia in cultured vascular endothelial cells. Tucci, M., Nygard, K., Tanswell, B.V., Farber, H.W., Hill, D.J., Han, V.K. J. Endocrinol. (1998) [Pubmed]
  3. Insulin-like growth factor binding protein production in bovine retinal endothelial cells. Giannini, S., Cresci, B., Manuelli, C., Fujita-Yamaguchi, Y., Romagnani, P., Mohan, S., Rotella, C.M. Metab. Clin. Exp. (1997) [Pubmed]
  4. The ontogeny of the somatotropic axis in Hereford calves from birth to one year of age and its response to administration of exogenous bovine somatotropin. Govoni, K.E., Hoagland, T.A., Zinn, S.A. J. Anim. Sci. (2004) [Pubmed]
  5. Regulation of endothelial IGFBP-3 synthesis and secretion by IGF-I and TGF-beta. Erondu, N.E., Dake, B.L., Moser, D.R., Lin, M., Boes, M., Bar, R.S. Growth Regul. (1996) [Pubmed]
  6. Growth regulation of prostatic stromal cells by prostate-specific antigen. Sutkowski, D.M., Goode, R.L., Baniel, J., Teater, C., Cohen, P., McNulty, A.M., Hsiung, H.M., Becker, G.W., Neubauer, B.L. J. Natl. Cancer Inst. (1999) [Pubmed]
  7. Insulin-like growth factor-I antagonizes the antiproliferative effects of cyclooxygenase-2 inhibitors on BxPC-3 pancreatic cancer cells. Levitt, R.J., Pollak, M. Cancer Res. (2002) [Pubmed]
  8. Transcriptional and posttranscriptional regulation of insulin-like growth factor binding protein-3 by cyclic adenosine 3',5'-monophosphate: messenger RNA stabilization is accompanied by decreased binding of a 42-kDa protein to a uridine-rich domain in the 3'-untranslated region. Erondu, N.E., Nwankwo, J., Zhong, Y., Boes, M., Dake, B., Bar, R.S. Mol. Endocrinol. (1999) [Pubmed]
  9. Temporal gene expression profiling of liver from periparturient dairy cows reveals complex adaptive mechanisms in hepatic function. Loor, J.J., Dann, H.M., Everts, R.E., Oliveira, R., Green, C.A., Guretzky, N.A., Rodriguez-Zas, S.L., Lewin, H.A., Drackley, J.K. Physiol. Genomics (2005) [Pubmed]
  10. Regulation of insulin-like growth factor binding protein-3 messenger ribonucleic acid expression by insulin-like growth factor I. Bale, L.K., Conover, C.A. Endocrinology (1992) [Pubmed]
  11. Enhanced expression of dihydrofolate reductase by bovine kidney epithelial cells results in altered cell morphology, IGF-I responsiveness, and IGF binding protein-3 expression. Cohick, W.S., Clemmons, D.R. J. Cell. Physiol. (1994) [Pubmed]
  12. Expression of insulin-like growth factor binding protein (IGFBP)-3, and the effects of IGFBP-2 and -3 in the bovine corpus luteum. Brown, T.A., Braden, T.D. Domest. Anim. Endocrinol. (2001) [Pubmed]
  13. The effect of an acute energy deficit on the hormone profile of dominant follicles in dairy cows. Comin, A., Gerin, D., Cappa, A., Marchi, V., Renaville, R., Motta, M., Fazzini, U., Prandi, A. Theriogenology (2002) [Pubmed]
  14. Stimulation of insulin-like growth factor (IGF) binding protein-3 synthesis by IGF-I and transforming growth factor-alpha is mediated by both phosphatidylinositol-3 kinase and mitogen-activated protein kinase pathways in mammary epithelial cells. Sivaprasad, U., Fleming, J., Verma, P.S., Hogan, K.A., Desury, G., Cohick, W.S. Endocrinology (2004) [Pubmed]
  15. Large variation in steroid concentrations and insulin-like growth factor binding proteins exists among individual small antral follicles collected from within cows at random stages of the estrous cycle. Roberts, A.J., Al-Hassan, M.J., Fricke, P.M., Echternkamp, S.E. J. Anim. Sci. (2006) [Pubmed]
  16. Insulin-like growth factor (IGF) system in the bovine mammary gland and milk. Baumrucker, C.R., Erondu, N.E. Journal of mammary gland biology and neoplasia. (2000) [Pubmed]
  17. Characterization of insulin-like growth factor-binding proteins in the uterus and conceptus during early conceptus elongation in cattle. Keller, M.L., Roberts, A.J., Seidel, G.E. Biol. Reprod. (1998) [Pubmed]
  18. Vascular endothelial growth factor and transforming growth factor-beta1 regulate the expression of insulin-like growth factor-binding protein-3, -4, and -5 in large vessel endothelial cells. Dahlfors, G., Arnqvist, H.J. Endocrinology (2000) [Pubmed]
  19. Growth hormone suppresses the expression of IGFBP-5, and promotes the IGF-I-induced phosphorylation of Akt in bovine mammary epithelial cells. Sakamoto, K., Yano, T., Kobayashi, T., Hagino, A., Aso, H., Obara, Y. Domest. Anim. Endocrinol. (2007) [Pubmed]
  20. Effects of age and estrogen status on the skeletal IGF regulatory system. Studies with human marrow. Rosen, C.J., Verault, D., Steffens, C., Cheleuitte, D., Glowacki, J. Endocrine (1997) [Pubmed]
  21. Regulation of IGF binding protein synthesis by a bovine mammary epithelial cell line. Cohick, W.S., Turner, J.D. J. Endocrinol. (1998) [Pubmed]
  22. Production of insulin-like growth factor binding-proteins by bovine adrenomedullary cells: differential regulation by IGF-I and dexamethasone. Grønning, M., Serck-Hanssen, G. Comp. Biochem. Physiol., Part A Mol. Integr. Physiol. (2003) [Pubmed]
  23. Regulation of insulin-like growth factor-binding proteins in serum and lymph of lactating cows by somatotropin. Cohick, W.S., McGuire, M.A., Clemmons, D.R., Bauman, D.E. Endocrinology (1992) [Pubmed]
  24. IGF-I mRNA levels in bovine satellite cell cultures: effects of fusion and anabolic steroid treatment. Kamanga-Sollo, E., Pampusch, M.S., Xi, G., White, M.E., Hathaway, M.R., Dayton, W.R. J. Cell. Physiol. (2004) [Pubmed]
  25. Insulin-like growth factor (IGF)-binding protein-3 blocks IGF-I-induced receptor down-regulation and cell desensitization in cultured bovine fibroblasts. Conover, C.A., Powell, D.R. Endocrinology (1991) [Pubmed]
  26. Secretory activity of bovine ovarian granulosa cells transfected with sense and antisense insulin-like growth factor (IGF) binding protein-3 and the response to IGF-I, GH, LH, oxytocin and oestradiol. Sirotkin, A.V., Makarevich, A.V., Corkins, M.R., Kotwica, J., Kwon, H.B., Bulla, J., Hetényi, L. J. Mol. Endocrinol. (2001) [Pubmed]
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