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Gene Review

IGF1  -  insulin-like growth factor 1 (somatomedin C)

Bos taurus

Synonyms: IGF-1, IGF-I
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Disease relevance of IGF1


Psychiatry related information on IGF1

  • Food deprivation for nearly 3 d decreased the levels of serum IGF-I by 63% (P < 0.01), and this decrease was associated with a 75% decrease (P < 0.01) in total IGF-I mRNA in the liver [6].
  • Thus, transforming growth factor-beta (TGF-beta) and insulin-like growth factor-1 (IGF-1), cytokines which independently maintain proteoglycan homeostasis (Morales and Roberts, 1988, J. Biol. Chem. 263, 828; and Luyten et al., 1988, Arch. Biochem. Biophys. 267, 416), were tested [7].
  • During the critical period of NEB in high yielding dairy cattle early postpartum, IGF-I concentrations are low in blood and its levels are positively correlated to energy status and reproductive function during this period [8].

High impact information on IGF1

  • However, oral toxicity studies have shown that bovine IGF-I lacks oral activity in rats [9].
  • Additionally, the concentration of IGF-I in milk of rbGH-treated cows is within the normal physiological range found in human breast milk, and IGF-I is denatured under conditions used to process cow's milk for infant formula [9].
  • For example, in 1% fetal bovine serum (FBS), trastuzumab reduced cell proliferation by 42% (P =.002); however, in 10% FBS or IGF-I, trastuzumab had no effect on proliferation [10].
  • We investigated whether insulin-like growth factor-I (IGF-I), which activates cell survival signals, interferes with the growth-inhibitory action of trastuzumab [10].
  • RESULTS: We observed a concentration-dependent proliferative response of BPH-derived stromal cells to IGF-I [11].

Chemical compound and disease context of IGF1

  • Suramin inhibits the growth of human rhabdomyosarcoma by interrupting the insulin-like growth factor II autocrine growth loop [12].
  • Production and characterization of recombinant insulin-like growth factor-I (IGF-I) and potent analogues of IGF-I, with Gly or Arg substituted for Glu3, following their expression in Escherichia coli as fusion proteins [13].
  • Plasma GH profiles and circulating concentrations of plasma insulin-like growth factors-I and -II (IGF-I and -II) were examined in 20 steers on either high (3% dry matter of body weight per day) or low (1% dry matter of body weight per day) planes of nutrition with or without an implant of oestradiol-17 beta [14].
  • The present study was conducted to elucidate whether progesterone affects IGF-I and its receptor expression in cultured leiomyoma cells [15].
  • Ingestion of small portions by calves avoided marked hyperglycemia and lactate increments, and lower plasma urea concentrations mirrored enhanced nitrogen utilization, possibly mediated by the altered growth hormone, IGF-I and insulin status [16].

Biological context of IGF1


Anatomical context of IGF1


Associations of IGF1 with chemical compounds


Physical interactions of IGF1

  • We have previously used tyrosine iodination to implicate Tyr-60 in the IGF-binding site of bovine IGFBP-2 (Hobba, G. D., Forbes, B. E., Parkinson, E. J., Francis, G. L., and Wallace, J. C. (1996) J. Biol. Chem. 271, 30529-30536) [26].
  • The percentage of the total IGF-I binding activity attributed to IGFBP-3 was greater (p < 0.05) in myometrium, serum, and uterine fluid (> 50%) than in inter- (40%) and intracaruncular (37%) endometrium [27].
  • Stimulation of circulating insulin-like growth factor I (IGF-I) and insulin-like growth factor binding proteins (IGFBP) due to administration of a combined trenbolone acetate and estradiol implant in feedlot cattle [28].
  • Residues 236-270 also appeared to play a role in determining IGF binding specificity as their removal resulted in mutants with higher IGF-II binding affinity [29].
  • In addition, early embryos express mRNAs encoding IGF-binding proteins (IGFBPs) 2-5 from the one-cell to the blastocyst stage and IGFBP5 mRNA at the blastocyst stage [30].

Enzymatic interactions of IGF1


Regulatory relationships of IGF1


Other interactions of IGF1

  • 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 [32].
  • As IGFs are secreted in large amounts by the female reproductive tract, it has been hypothesized that maternal IGFs may affect embryonic growth and differentiation in a fine-tuned manner, involving modulation of IGF effects by embryonic IGFBP and IGF-I-R expression [37].
  • Embryonic IGFBP-2 mRNA levels in the LR(3) treatment group were 1.7-fold (P < 0.001) and 2.8-fold (P < 0.001) higher than those in the IGF-I and control groups, respectively [37].
  • These results demonstrate that the food deprivation-induced decrease in circulating IGF-I in steers is associated with a coordinate decrease in the expression of different IGF-I mRNA variants and a specific decrease in the expression of GHR mRNA variants 1C3 and 1A in the liver [6].
  • IGF-I acted to decrease apoptosis and increase total cell number and IGF-II increased cell number alone [38].

Analytical, diagnostic and therapeutic context of IGF1

  • Subsequently, the mixture of free IGF and IGF.bIGFBP-2 complex was resolved by neutral chromatography, and the IGF component of the complex with bIGFBP-2 was recovered by reverse-phase high performance liquid chromatography at pH 2 [20].
  • Kinetic analysis of the bIGFBP-2 mutants on IGF biosensor chips in the BIAcore instrument revealed that Tyr-60 --> Phe bIGFBP-2 bound to the IGF-I surface 3.0-fold more slowly than bIGFBP-2 and was released 2.6-fold more rapidly than bIGFBP-2 [26].
  • 1. The tyrosine labeling patterns of the two populations of IGF, one iodinated while free and the other iodinated while associated with binding protein, were determined following endoproteinase Glu-C peptide mapping [20].
  • Total cell numbers of blastocysts were highest in the presence of LR(3) (105 +/- 4), followed by IGF-I (96 +/- 5), and the control group (91 +/- 3; P < 0.05) [37].
  • Northern blotting of total RNA and ligand blot and immunoblot analyses of serum-free conditioned medium revealed that Caco-2 cells produce several IGF binding proteins (IGFBPs), including IGFBP-2, -3, and -4, as well as a 31,000 M(r) species that was not identified [1].


  1. Expression of insulin-like growth factor-II and insulin-like growth factor binding proteins during Caco-2 cell proliferation and differentiation. Park, J.H., Corkins, M.R., Vanderhoof, J.A., Caruso, N.M., Hrbek, M.J., Schaffer, B.S., Slentz, D.H., McCusker, R.H., MacDonald, R.G. J. Cell. Physiol. (1996) [Pubmed]
  2. Expression of messenger RNAs encoding insulin-like growth factor-I, -II, and insulin-like growth factor binding protein-2 in bovine endometrium during the estrous cycle and early pregnancy. Geisert, R.D., Lee, C.Y., Simmen, F.A., Zavy, M.T., Fliss, A.E., Bazer, F.W., Simmen, R.C. Biol. Reprod. (1991) [Pubmed]
  3. Expression of the components of the insulin-like growth factor axis across the growth-plate. Olney, R.C., Mougey, E.B. Mol. Cell. Endocrinol. (1999) [Pubmed]
  4. 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]
  5. Endocrine events prior to puberty in heifers: role of somatotropin, insulin-like growth factor-I and insulin-like growth factor binding proteins. Armstrong, J.D., Stanko, R.L., Cohick, W.S., Simpson, R.B., Harvey, R.W., Huff, B.G., Clemmons, D.R., Whitacre, M.D., Campbell, R.M., Heimer, E.P. J. Physiol. Pharmacol. (1992) [Pubmed]
  6. Reduced serum insulin-like growth factor (IGF) I is associated with reduced liver IGF-I mRNA and liver growth hormone receptor mRNA in food-deprived cattle. Wang, Y., Eleswarapu, S., Beal, W.E., Swecker, W.S., Akers, R.M., Jiang, H. J. Nutr. (2003) [Pubmed]
  7. Transforming growth factor-beta and insulin-like growth factor-1 restore proteoglycan metabolism of bovine articular cartilage after depletion by retinoic acid. Morales, T.I. Arch. Biochem. Biophys. (1994) [Pubmed]
  8. Insulin-like growth factor-I as a possible hormonal mediator of nutritional regulation of reproduction in cattle. Zulu, V.C., Nakao, T., Sawamukai, Y. J. Vet. Med. Sci. (2002) [Pubmed]
  9. Bovine growth hormone: human food safety evaluation. Juskevich, J.C., Guyer, C.G. Science (1990) [Pubmed]
  10. Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin). Lu, Y., Zi, X., Zhao, Y., Mascarenhas, D., Pollak, M. J. Natl. Cancer Inst. (2001) [Pubmed]
  11. 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]
  12. Suramin inhibits the growth of human rhabdomyosarcoma by interrupting the insulin-like growth factor II autocrine growth loop. Minniti, C.P., Maggi, M., Helman, L.J. Cancer Res. (1992) [Pubmed]
  13. Production and characterization of recombinant insulin-like growth factor-I (IGF-I) and potent analogues of IGF-I, with Gly or Arg substituted for Glu3, following their expression in Escherichia coli as fusion proteins. King, R., Wells, J.R., Krieg, P., Snoswell, M., Brazier, J., Bagley, C.J., Wallace, J.C., Ballard, F.J., Ross, M., Francis, G.L. J. Mol. Endocrinol. (1992) [Pubmed]
  14. Influence of nutritional status and oestradiol-17 beta on plasma growth hormone, insulin-like growth factors-I and -II and the response to exogenous growth hormone in young steers. Breier, B.H., Gluckman, P.D., Bass, J.J. J. Endocrinol. (1988) [Pubmed]
  15. Progesterone down-regulates insulin-like growth factor-I expression in cultured human uterine leiomyoma cells. Yamada, T., Nakago, S., Kurachi, O., Wang, J., Takekida, S., Matsuo, H., Maruo, T. Hum. Reprod. (2004) [Pubmed]
  16. Postprandial metabolism and endocrine status in veal calves fed at different frequencies. Kaufhold, J.N., Hammon, H.M., Bruckmaier, R.M., Breier, B.H., Blum, J.W. J. Dairy Sci. (2000) [Pubmed]
  17. Effects of polymorphic microsatellites in the regulatory region of IGF1 and GHR on growth and carcass traits in beef cattle. Curi, R.A., Oliveira, H.N., Silveira, A.C., Lopes, C.R. Anim. Genet. (2005) [Pubmed]
  18. Analysis of population differentiation in North Eurasian cattle (Bos taurus) using single nucleotide polymorphisms in three genes associated with production traits. Li, M.H., Adamowicz, T., Switonski, M., Ammosov, I., Ivanova, Z., Kiselyova, T., Popov, R., Kantanen, J. Anim. Genet. (2006) [Pubmed]
  19. The insulin-like growth factor (IGF) binding site of bovine insulin-like growth factor binding protein-2 (bIGFBP-2) probed by iodination. Hobba, G.D., Forbes, B.E., Parkinson, E.J., Francis, G.L., Wallace, J.C. J. Biol. Chem. (1996) [Pubmed]
  20. Insulin-like growth factor (IGF)-I and IGF-II binding to an IGF binding protein. An investigation using chemical modification of tyrosine residues as a structural probe for the sites of interaction. Moss, J.A., Francis, G.L., Ross, M., Wallace, J.C., Ballard, F.J. J. Biol. Chem. (1991) [Pubmed]
  21. Maturation medium supplements affect transcript level of apoptosis and cell survival related genes in bovine blastocysts produced in vitro. Warzych, E., Wrenzycki, C., Peippo, J., Lechniak, D. Mol. Reprod. Dev. (2007) [Pubmed]
  22. Levels of insulin-like growth factor (IGF) binding proteins, luteinizing hormone and IGF-I receptors, and steroids in dominant follicles during the first follicular wave in cattle exhibiting regular estrous cycles. Stewart, R.E., Spicer, L.J., Hamilton, T.D., Keefer, B.E., Dawson, L.J., Morgan, G.L., Echternkamp, S.E. Endocrinology (1996) [Pubmed]
  23. Production and hormonal regulation of insulin-like growth factor binding proteins in bovine chondrocytes. Olney, R.C., Smith, R.L., Kee, Y., Wilson, D.M. Endocrinology (1993) [Pubmed]
  24. Identification of insulin-like growth factor binding proteins from cultured human epidermal keratinocytes. Murashita, M.M., Russo, V.C., Edmondson, S.R., Wraight, C.J., Werther, G.A. J. Cell. Physiol. (1995) [Pubmed]
  25. 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]
  26. Alanine screening mutagenesis establishes tyrosine 60 of bovine insulin-like growth factor binding protein-2 as a determinant of insulin-like growth factor binding. Hobba, G.D., Löthgren, A., Holmberg, E., Forbes, B.E., Francis, G.L., Wallace, J.C. J. Biol. Chem. (1998) [Pubmed]
  27. 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]
  28. Stimulation of circulating insulin-like growth factor I (IGF-I) and insulin-like growth factor binding proteins (IGFBP) due to administration of a combined trenbolone acetate and estradiol implant in feedlot cattle. Johnson, B.J., Hathaway, M.R., Anderson, P.T., Meiske, J.C., Dayton, W.R. J. Anim. Sci. (1996) [Pubmed]
  29. Localization of an insulin-like growth factor (IGF) binding site of bovine IGF binding protein-2 using disulfide mapping and deletion mutation analysis of the C-terminal domain. Forbes, B.E., Turner, D., Hodge, S.J., McNeil, K.A., Forsberg, G., Wallace, J.C. J. Biol. Chem. (1998) [Pubmed]
  30. IGF paracrine and autocrine interactions between conceptus and oviduct. Watson, A.J., Westhusin, M.E., Winger, Q.A. J. Reprod. Fertil. Suppl. (1999) [Pubmed]
  31. Activation of a microtubule-associated protein-2 kinase by insulin-like growth factor-I in bovine chromaffin cells. Cahill, A.L., Perlman, R.L. J. Neurochem. (1991) [Pubmed]
  32. 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]
  33. Regulation of IGF binding protein synthesis by a bovine mammary epithelial cell line. Cohick, W.S., Turner, J.D. J. Endocrinol. (1998) [Pubmed]
  34. Pretreatment with bovine growth hormone is as effective as treatment during metabolic stress to reduce catabolism in fasted lambs. Ogawa, E., Breier, B.H., Bauer, M.K., Gallaher, B.W., Grant, P.A., Walton, P.E., Owens, J.A., Gluckman, P.D. Endocrinology (1996) [Pubmed]
  35. Insulin-like growth factor (IGF)-binding protein-4 proteolytic degradation in bovine, equine, and porcine preovulatory follicles: regulation by IGFs and heparin-binding domain-containing peptides. Mazerbourg, S., Zapf, J., Bar, R.S., Brigstock, D.R., Monget, P. Biol. Reprod. (2000) [Pubmed]
  36. Fibronectin fragments upregulate insulin-like growth factor binding proteins in chondrocytes. Purple, C.R., Untermann, T.G., Pichika, R., Homandberg, G.A. Osteoarthr. Cartil. (2002) [Pubmed]
  37. Insulin-like growth factor I (IGF-I) and long R(3)IGF-I differently affect development and messenger ribonucleic acid abundance for IGF-binding proteins and type I IGF receptors in in vitro produced bovine embryos. Prelle, K., Stojkovic, M., Boxhammer, K., Motlik, J., Ewald, D., Arnold, G.J., Wolf, E. Endocrinology (2001) [Pubmed]
  38. Regulation of apoptosis in the bovine blastocyst by insulin and the insulin-like growth factor (IGF) superfamily. Byrne, A.T., Southgate, J., Brison, D.R., Leese, H.J. Mol. Reprod. Dev. (2002) [Pubmed]
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