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IGFBP2  -  insulin-like growth factor binding protein...

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Disease relevance of IGFBP-2

  • IUGR increased hepatic IGF-binding protein (IGFBP)-1 and placental IGFBP-2 and -3 mRNA levels with no further effect of GH infusion [1].
  • In fetal sheep, prolonged hypoxia (for 24 h) induced by a reduction in maternal uterine artery blood flow, increases insulin-like growth factor binding protein-1 (IGFBP-1) levels and decreases IGFBP-2 levels in the plasma, with corresponding changes in messenger RNA (mRNA) levels in the liver [2].

High impact information on IGFBP-2

  • Plasma IGFBP-2 content was significantly reduced in prenatal T-treated newborns, but by 4 months these females had significantly higher circulating IGF-I and IGFBP-3 concentrations and faster growth rates than control females [3].
  • This was associated with a rapid rise in IGFBP-1 (P < 0.001), but no change in IGF-II or IGFBP-2 [4].
  • The release of IGFBP-2 and IGFBP-5 were also potentiated without changes to steady state mRNA, and for IGFBP-5 this was due in part to a release from the cell membrane in the presence of IGF-II [5].
  • The addition of an excess of IGF-I enhanced IGFBP-4 proteolytic degradation, whereas addition of IGFBP-2 or -3 or monoclonal antibodies against IGF-I and -II dose dependently inhibited IGFBP-4 proteolytic degradation [6].
  • The aim of this work was to study the relationship between apoptosis induced by serum starvation in vitro and expression of IGFBP-2 and -5 by ovine granulosa cells [7].

Biological context of IGFBP-2


Anatomical context of IGFBP-2

  • In addition, IGFBP-2 mRNA levels were decreased in the liver (50%) and kidney (30%) of hypoxic fetuses [11].
  • These data suggest that in early atretic follicles, the increase in IGFBP-2 participates in the decrease in IGFBP-4 degradation [6].
  • IGF-binding protein-2 (IGFBP-2 mRNA was not detected until day 29 of gestation, when it appeared restricted to the dense caruncular-like stroma lining the luminal epithelium, colocalized with IGFBP-4 [13].
  • We conclude that inhibition of thyroid iodide uptake and its organification, stimulation of iodocompound secretion and stimulation of IGFBP-2 and IGFBP-3 secretion may be effected through the modulation of a limited number of PKC isozymes and possibly initially, only through PKC beta 1 [14].
  • In anterior pituitary glands, IGFBP-2 tended to be higher in LOW-BCS than in HIGH-BCS ewes [15].

Associations of IGFBP-2 with chemical compounds

  • Ethanol exposure did not alter maternal or fetal plasma concentrations of IGFBP-2 and IGFBP-3, measured by Western ligand blotting [16].
  • Insulin (16.7 or 167 nM) selectively increased mRNA and the release of IGFBP-3, while cortisol (1 or 5 microM) inhibited both mRNA and release of IGFBP-2 and IGFBP-5 [5].
  • In response to estradiol, pituitary IGFBP-2 tended to increase and mRNA for IGFBP-2 increased twofold [17].
  • IGFBP-2, -3 and -4 mRNAs were all present at low concentrations in the corpus luteum (OD 0.04 +/- 0.005, n = 6; 0.05 +/- 0.02, n = 5; 0.1 +/- 0.02, n = 8 respectively), whereas only IGFBP-2 and -4 mRNAs were found in ovarian stroma (OD 0.04 +/- 0.006, n = 4; 0.04 +/- 0.007, n = 9 respectively) [18].
  • There was no significant difference, however, in the adrenal expression of the cyclin-kinase inhibitory proteins (p16ink or p21Cip) or in the IGF system (IGF-II, IGFBP-2 or IGF1R) mRNA between metyrapone- and vehicle-infused [19].

Regulatory relationships of IGFBP-2


Other interactions of IGFBP-2


Analytical, diagnostic and therapeutic context of IGFBP-2

  • Southern blot analysis of ovine genomic DNA with the cDNA probe demonstrated that IGFBP-2 is encoded by a single gene [9].
  • The proteins of 34 and 19 kDa were immunopositive on Western blot analysis using anti-bovine IGFBP-2 antiserum [24].
  • Radioimmunoassay of IGFBP-2 showed that while GH treatment reduced the plasma content of IGFBP-2 by about half, the lymph:plasma ratio was increased from 0.68 to 0.87 [25].
  • Northern blot analysis of endometrial total RNA revealed major transcripts for IGF-I (7.1 kb), IGF-II (5.8 kb), IGFBP-1 (1.3 kb) and IGFBP-2 (1.7 kb) [26].
  • Adrenal IGF-II mRNA levels were lower (P<0.05) in the PR group, however, adrenal IGFBP-2 mRNA levels were not different between the PR and control groups [27].


  1. Effect of pulsatile growth hormone administration to the growth-restricted fetal sheep on somatotrophic axis gene expression in fetal and placental tissues. Bloomfield, F.H., van Zijl, P.L., Bauer, M.K., Phua, H.H., Harding, J.E. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  2. Catecholamines stimulate the synthesis and release of insulin-like growth factor binding protein-1 (IGFBP-1) by fetal sheep liver in vivo. Hooper, S.B., Bocking, A.D., White, S.E., Fraher, L.J., McDonald, T.J., Han, V.K. Endocrinology (1994) [Pubmed]
  3. Prenatal exposure to excess testosterone modifies the developmental trajectory of the insulin-like growth factor system in female sheep. Crespi, E.J., Steckler, T.L., Mohankumar, P.S., Padmanabhan, V. J. Physiol. (Lond.) (2006) [Pubmed]
  4. Differential changes in insulin-like growth factors and their binding proteins following asphyxia in the preterm fetal sheep. Bennet, L., Oliver, M.H., Gunn, A.J., Hennies, M., Breier, B.H. J. Physiol. (Lond.) (2001) [Pubmed]
  5. Expression and release of insulin-like growth factor binding proteins in isolated epiphyseal growth plate chondrocytes from the ovine fetus. De Los Rios, P., Hill, D.J. J. Cell. Physiol. (2000) [Pubmed]
  6. Insulin-like growth factor binding protein-4 proteolytic degradation in ovine preovulatory follicles: studies of underlying mechanisms. Mazerbourg, S., Zapf, J., Bar, R.S., Brigstock, D.R., Lalou, C., Binoux, M., Monget, P. Endocrinology (1999) [Pubmed]
  7. Expression of insulin-like growth factor binding protein-5 by ovine granulosa cells is regulated by cell density and programmed cell death in vitro. Monget, P., Pisselet, C., Monniaux, D. J. Cell. Physiol. (1998) [Pubmed]
  8. Altered Placental and Fetal Expression of IGFs and IGF-Binding Proteins Associated With Intrauterine Growth Restriction in Fetal Sheep During Early and Mid-Pregnancy. DE Vrijer, B., Davidsen, M.L., Wilkening, R.B., Anthony, R.V., Regnault, T.R. Pediatr. Res. (2006) [Pubmed]
  9. The characterization and expression of ovine insulin-like growth factor-binding protein-2. Delhanty, P.J., Han, V.K. J. Mol. Endocrinol. (1992) [Pubmed]
  10. The expression of insulin-like growth factor (IGF)-binding protein-2 and IGF-II genes in the tissues of the developing ovine fetus. Delhanty, P.J., Han, V.K. Endocrinology (1993) [Pubmed]
  11. Prolonged hypoxia induced by the reduction of maternal uterine blood flow alters insulin-like growth factor-binding protein-1 (IGFBP-1) and IGFBP-2 gene expression in the ovine fetus. McLellan, K.C., Hooper, S.B., Bocking, A.D., Delhanty, P.J., Phillips, I.D., Hill, D.J., Han, V.K. Endocrinology (1992) [Pubmed]
  12. Localization of insulin-like growth factor-I (IGF-I) and -II messenger ribonucleic acid and type 1 IGF receptors in the ovine uterus during the estrous cycle and early pregnancy. Stevenson, K.R., Gilmour, R.S., Wathes, D.C. Endocrinology (1994) [Pubmed]
  13. Pregnancy-specific alterations in the expression of the insulin-like growth factor system during early placental development in the ewe. Reynolds, T.S., Stevenson, K.R., Wathes, D.C. Endocrinology (1997) [Pubmed]
  14. Phorbol esters showing selective activation of PKC isozymes in vitro regulate thyroid function and insulin-like growth factor binding protein secretion. Eggo, M.C., Sheppard, M.C., Evans, F.J., Lord, J.M. Cell. Signal. (1994) [Pubmed]
  15. Insulin-like growth factor-I, insulin-like growth factor-binding proteins, and gonadotropins in the hypothalamic-pituitary axis and serum of nutrient-restricted ewes. Snyder, J.L., Clapper, J.A., Roberts, A.J., Sanson, D.W., Hamernik, D.L., Moss, G.E. Biol. Reprod. (1999) [Pubmed]
  16. Acute ethanol exposure in pregnancy alters the insulin-like growth factor axis of fetal and maternal sheep. Gatford, K.L., Dalitz, P.A., Cock, M.L., Harding, R., Owens, J.A. Am. J. Physiol. Endocrinol. Metab. (2007) [Pubmed]
  17. Estradiol increases relative amounts of insulin-like growth factor binding protein (IGFBP)-3 in serum and expression of IGFBP-2 in anterior pituitaries of ewes. Clapper, J.A., Snyder, J.L., Roberts, A.J., Hamernik, D.L., Moss, G.E. Biol. Reprod. (1998) [Pubmed]
  18. Expression of mRNAs for insulin-like growth factor binding proteins-2, -3 and -4 in the ovine ovary throughout the oestrous cycle. Perks, C.M., Wathes, D.C. J. Endocrinol. (1996) [Pubmed]
  19. Metyrapone infusion stimulates adrenal growth without activating the cell cycle or the IGF system in the late gestation fetal sheep. Warnes, K.E., McMillen, I.C., Robinson, J.S., Coulter, C.L. Endocr. Res. (2004) [Pubmed]
  20. Body growth, carcass composition, and endocrine changes in lambs chronically treated with recombinantly derived insulin-like growth factor-I. Cottam, Y.H., Blair, H.T., Gallaher, B.W., Purchas, R.W., Breier, B.H., McCutcheon, S.N., Gluckman, P.D. Endocrinology (1992) [Pubmed]
  21. Growth hormone stimulates the secretion of insulin-like growth factor binding protein-2 (IGFBP-2) by monolayer cultures of sheep costal growth plate chondrocytes. Borromeo, V., Bramani, S., Holder, A.T., Carter, C., Secchi, C., Beattie, J. Mol. Cell. Biochem. (1996) [Pubmed]
  22. Regulation of insulin-like growth factor-binding protein-5 by insulin-like growth factor I and interleukin-1alpha in ovine articular chondrocytes. Sunic, D., McNeil, J.D., Rayner, T.E., Andress, D.L., Belford, D.A. Endocrinology (1998) [Pubmed]
  23. Effect of a high maternal dietary intake during mid-gestation on components of the utero-placental insulin-like growth factor (IGF) system in adolescent sheep with retarded placental development. Gadd, T.S., Aitken, R.P., Wallace, J.M., Wathes, D.C. J. Reprod. Fertil. (2000) [Pubmed]
  24. Hormonal regulation of insulin-like growth factor (IGF)-binding proteins secreted by isolated sheep thyroid epithelial cells: relationship with iodine organification. Wang, J.F., Becks, G.P., Hanada, E., Buckingham, K.D., Phillips, I.D., Hill, D.J. J. Endocrinol. (1991) [Pubmed]
  25. Effect of growth hormone treatment on the distribution of insulin-like growth factor-I between plasma and lymph of lactating sheep. Davis, S.R., Hodgkinson, S.C., Prosser, C.G., Gluckman, P.D., Buonomo, F.C., Collier, R.J. J. Endocrinol. (1992) [Pubmed]
  26. Endometrial expression of mRNA encoding insulin-like growth factors I and II and IGF-binding proteins 1 and 2 in early pregnant ewes. Cann, C.H., Fairclough, R.J., Sutton, R., Gow, C.B. J. Reprod. Fertil. (1997) [Pubmed]
  27. Differential effects of placental restriction on IGF-II, ACTH receptor and steroidogenic enzyme mRNA levels in the foetal sheep adrenal. Ross, J.T., Phillips, I.D., Simonetta, G., Owens, J.A., Robinson, J.S., McMillen, I.C. J. Neuroendocrinol. (2000) [Pubmed]
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