Disease relevance of IGF1

• The components of the insulin-like growth factor (IGF) axis and their roles in regulating proliferation and differentiation of the human colon adenocarcinoma cell line, Caco-2, have been investigated [1].
• Concentrations of IGF-I and IGF-II in uterine flushings were greater on Days 0 and 5 than on other days of the estrous cycle or pregnancy [2].
• Since IGF-I and -II are potent stimulators of proliferation, the down-regulation of these genes may be necessary in order for hypertrophy to proceed [3].
• IGF-I peptide and mRNA levels were very low in both cell types, and decreased further with exposure to hypoxia [4].
• Delayed puberty was preceded by suppression of follicular growth, and decreased concentrations of IGF-I in serum and follicular fluid.(ABSTRACT TRUNCATED AT 400 WORDS)[5]

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

• The IGF1 microsatellite allele substitutions of 229 for 225 within Nellore group and of 225 for 229 within 1/2 Angus were not significant for any of the traits [17].
• Allele frequencies of IGF1 exhibited significant (P < 0.05) deviation from neutral expectation and therefore, might be associated with divergence in North Eurasian cattle because of genetic selection [18].
• Effects of polymorphic microsatellites in the regulatory region of IGF1 and GHR on growth and carcass traits in beef cattle [17].
• The insulin-like growth factor (IGF) binding site of bovine insulin-like growth factor binding protein-2 (bIGFBP-2) probed by iodination [19].
• Sites of interaction between the binding protein and IGF were then probed by iodination of the available tyrosine residues [20].

Anatomical context of IGF1

• No transcript of IGF1 gene was detected either in oocytes or in blastocysts [21].
• Numbers of IGF-I receptors in granulosa cells were unaffected by size or growth of follicles, but were severalfold greater than in theca cells [22].
• Production and hormonal regulation of insulin-like growth factor binding proteins in bovine chondrocytes [23].
• Keratinocyte-derived IGFBPs are likely to play a role in the transport and targeting of IGF-I from dermally derived fibroblasts to the epidermis [24].
• Insulin-like growth factor binding protein-2 mediates the inhibition of DNA synthesis by transforming growth factor-beta in mink lung epithelial cells [25].

Associations of IGF1 with chemical compounds

• To examine the role of IGF tyrosine residues in the association with bIGFBP-2, we prepared nonradioactive 127I-labeled oIGF-II [20].
• We therefore propose that the hydroxyl group of Tyr-60 participates in a hydrogen bond that is important for the initial complex formation with IGF-I and the stabilization of this complex [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 [26].
• Concentrations of progesterone and IGF-I did not differ (P > 0.10) among follicle classes, but both were greater (P < 0.10) in late LG compared with early LG follicles [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 [22].

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

• The IGF-I-activated kinase also phosphorylated myelin basic protein, but had little or no activity toward histones or ribosomal S6 protein [31].

Regulatory relationships of IGF1

• However, the regulatory mechanisms responsible for IGF-induced increases in IGFBP-3 are unclear [32].
• In addition, the differential regulation of IGFBP-2, -3 and -6 by retinoic acid (which inhibits proliferation) and IGF-I (which stimulates proliferation) suggests that these forms of IGFBP have different roles in regulating mammary epithelial cell physiology [33].
• Plasma IGF-II levels were decreased by rbGH treatment during the well fed phase, but the responses to treatment during the fasted phase were variable, suggesting that plasma IGF-II is regulated in a different manner than plasma IGF-I [34].
• An excess of IGF-I enhanced IGFBP-4 degradation [35].
• Fibronectin fragments upregulate insulin-like growth factor binding proteins in chondrocytes [36].

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].

References