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Gene Review

IGFBP1  -  insulin-like growth factor binding protein 1

Ovis aries

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Disease relevance of IGFBP-1


High impact information on IGFBP-1

  • These findings provide evidence that prenatal T excess programmes the developmental trajectory of the IGF/IGFBP system in female sheep to reduce IGF bioavailability during IUGR and increase IGF bioavailability during prepubertal catch-up growth [2].
  • This was associated with a rapid rise in IGFBP-1 (P < 0.001), but no change in IGF-II or IGFBP-2 [5].
  • The results suggest that IGFBP expression and release within the developing growth plate can be modulated by IGF-II and other trophic factors, thus controlling IGF availability and action [6].
  • Neither growth hormone (GH), fibroblast growth factor-2, nor thyroxine (T(4)) had any effect on IGFBP expression or release [6].
  • Other heparin-binding domain-containing peptides derived from the connective tissue growth factor (CTGF) and from proteins not related to IGFBP, heparan/heparin interacting protein (HIP) and vitronectin, but not from p36 subunit of annexin II tetramer, inhibited IGFBP-4 degradation [7].

Chemical compound and disease context of IGFBP-1

  • Norepinephrine and epinephrine infusions increased IGFBP-1 levels significantly (2- to 5-fold) in fetal plasma within 8-12 h, and the time course pattern of elevation of plasma IGFBP-1 levels was similar to that observed in prolonged hypoxia [8].

Biological context of IGFBP-1

  • In contrast, IGF binding protein 1 (IGFBP-1) mRNA expression was higher (P < 0.05) and IGFBP-3 mRNA expression was lower (P < 0.05) in the endometrial glands of ewes in HH and MH groups [9].
  • Because the anatomical distribution of IGFBPs is likely to dictate IGF bioavailability, we determined the cellular distribution and expression of IGF-I, IGF-II, and IGFBP-1 to IGFBP-6 in epiphyseal growth plates of the fetal sheep, using immunocytochemistry and in situ hybridization [10].
  • Our findings suggest that locally produced IGF-II and IGF-I derived from the circulation can influence fetal epiphyseal chondrogenesis, and that this may be modulated locally by multiple IGFBP expression [10].
  • Placental and fetal development in lean ewes may be promoted by reduced IGFBP expression in the placentomes and enhanced UTMP production by the endometrial glands [11].
  • No significant changes were observed in plasma IGF-I and -II concentrations or IGFBP-1, -2, -3 or -4 levels throughout the 4-day study at either gestational age [12].

Anatomical context of IGFBP-1

  • RT-PCR analyses detected expression of IGFBPs (3, 4, 5 and 6) as well as PAPP-A mRNAs in the uterus, but not IGFBP-1 and IGFBP-2 mRNAs [13].
  • IGFBP immunoreactivity again appeared in hypertrophic chondrocytes [10].
  • Since IGFBP-1 synthesis in liver cells in vitro is stimulated by compounds that increase intracellular cAMP concentrations, we hypothesized that the increased IGFBP-1 synthesis during prolonged hypoxemia may be induced by circulating catecholamines, that are released during hypoxia, and that elevate fetal liver cAMP levels [8].
  • In conclusion, the location of the IGFBP-1 suggests that it may play a role in regulating the transfer of IGFs between the endometrium and the uterine lumen [14].
  • IGFBP-1 mRNA was confined to the luminal epithelium, with a highly significant variation in concentration according to the stage of the cycle [14].

Associations of IGFBP-1 with chemical compounds


Other interactions of IGFBP-1

  • These data show that each of the IGF carrier proteins is sensitive of changes in nutrition, either acutely, such as IGFBP-1, or chronically, as for IGFBP-3 [17].
  • Analysis of the time course of changes in plasma revealed that the changes in IGFBP-1 and IGFBP-2 occurred within 4 h of hypoxia.(ABSTRACT TRUNCATED AT 400 WORDS)[1]
  • In vivo, in the sheep ovary, the expression of insulin-like growth factor binding protein (IGFBP)-2 and particularly IGFBP-5 has been shown to increase dramatically in apoptotic granulosa cells from atretic follicles [18].
  • This was accompanied by changes in placental VEGF and IGFBP expression [19].
  • Components of the IGF system in medium-sized estrogenic follicles were similar in all treatment groups; however, in large estrogenic follicles rGH increased IGF-1 concentrations (P < 0.05) and intensity of the 44-42 kDa IGFBP band (P < 0.01) [20].

Analytical, diagnostic and therapeutic context of IGFBP-1


  1. 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]
  2. 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]
  3. The effect of a chronic maternal cortisol infusion on the late-gestation fetal sheep. Jensen, E.C., Gallaher, B.W., Breier, B.H., Harding, J.E. J. Endocrinol. (2002) [Pubmed]
  4. The risk of myocardial infarction is enhanced by a synergistic interaction between serum insulin and smoking. Bennet, A.M., Brismar, K., Hallqvist, J., Reuterwall, C., De Faire, U. Eur. J. Endocrinol. (2002) [Pubmed]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. 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]
  10. Cellular localization and expression of insulin-like growth factors (IGFs) and IGF binding proteins within the epiphyseal growth plate of the ovine fetus: possible functional implications. de los Rios, P., Hill, D.J. Can. J. Physiol. Pharmacol. (1999) [Pubmed]
  11. Effect of maternal body condition on placental and fetal growth and the insulin-like growth factor axis in Dorset ewes. Osgerby, J.C., Gadd, T.S., Wathes, D.C. Reproduction (2003) [Pubmed]
  12. The effect of intermittent umbilical cord occlusion on insulin-like growth factors and their binding proteins in preterm and near-term ovine fetuses. Green, L.R., Kawagoe, Y., Hill, D.J., Richardson, B.S., Han, V.K. J. Endocrinol. (2000) [Pubmed]
  13. The IGF system in the neonatal ovine uterus. Hayashi, K., Carpenter, K.D., Welsh, T.H., Burghardt, R.C., Spicer, L.J., Spencer, T.E. Reproduction (2005) [Pubmed]
  14. Expression of insulin-like growth factor binding protein-1 (IGFBP-1) mRNA in the ovine uterus throughout the oestrous cycle and early pregnancy. Osgerby, J.C., Gadd, T.S., Wathes, D.C. J. Endocrinol. (1999) [Pubmed]
  15. 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]
  16. 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]
  17. Circulating insulin-like growth factor II/mannose-6-phosphate receptor and insulin-like growth factor binding proteins in fetal sheep plasma are regulated by glucose and insulin. Gallaher, B.W., Oliver, M.H., Eichhorn, K., Kessler, U., Kiess, W., Harding, J.E., Gluckman, P.D., Breier, B.H. Eur. J. Endocrinol. (1994) [Pubmed]
  18. 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]
  19. The effects of acute nutrient restriction in the mid-gestational ewe on maternal and fetal nutrient status, the expression of placental growth factors and fetal growth. McMullen, S., Osgerby, J.C., Milne, J.S., Wallace, J.M., Wathes, D.C. Placenta (2005) [Pubmed]
  20. Growth hormone priming as an adjunct treatment in superovulatory protocols in the ewe alters follicle development but has no effect on ovulation rate. Joyce, I.M., Khalid, M., Haresign, W. Theriogenology (1998) [Pubmed]
  21. 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]
  22. Purification and assay of insulin-like growth factor-binding protein-1: measurement of circulating levels throughout pregnancy. Wang, H.S., Perry, L.A., Kanisius, J., Iles, R.K., Holly, J.M., Chard, T. J. Endocrinol. (1991) [Pubmed]
  23. 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]
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