Disease relevance of IGFBP2

• More moderate undernutrition (80% of requirements) did not affect circulating IGFBP-2 but did alter the response of IGFBP-2 to bST [1].
• The cDNA for bovine IGFBP-2 was inserted between regions coding for the pelB signal sequence and geneIII product, g3p, of bacteriophage fd in a phagemid vector to generate pGF14 [2].
• Furthermore, circulating IGFBP-2 appears to be higher in heifers than in bulls, and also appears to be negatively correlated with body weights [3].
• Thus IGFBP-2 can be secreted in E. coli and displayed on filamentous phage [2].
• On the other hand, IGFBP-2 was a potent inhibitor of IGF-II action in human breast and ovarian carcinoma cells [4].

High impact information on IGFBP2

• 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) [5].
• FSH inhibited the expression of IGFBP-2 mRNA in granulosa cells, whereas LH stimulated IGFBP-4 mRNA expression in theca cells [6].
• The regulation of IGFBP-2 and -4 mRNA expression in granulosa and theca cells was analyzed using a serum-free cell culture system [6].
• We conclude that low amounts of IGFBP-2 and increased thecal binding sites for hCG/LH appear to be related to establishment of the dominant follicle during the first follicular wave in cattle exhibiting regular estrous cycles during late lactation [7].
• Thus, RA is a potent but transient inhibitor of bovine mammary epithelial cell proliferation, and this growth inhibition is correlated with increased IGFBP-2 accumulation and inhibition of IGF-I stimulated IGFBP-3 protein secretion [8].

Biological context of IGFBP2

• Immunolocalization studies showed that spatial and temporal patterns of expression of IGFBP-2 and -3 were markedly altered in the placentomes of NT pregnancies compared to AI/IVP controls [9].
• The opposite pattern of IGFBP-2 gene expression in SF and some NRF may lead to follicular atresia [10].
• In conclusion, the reduced expression of IGFBP-2 mRNA in severe NEB cows may alter the bioavailability of circulating IGF-I and locally produced IGF-II to modulate the pre-recruitment stages of follicles required to maintain normal post partum ovarian cyclicity [11].
• The predicted protein sequence shares extensive sequence similarity with both the rat (82%) and human (89%) IGFBP-2s, so that the MDBK binding protein is clearly the bovine counterpart of IGFBP-2 [12].
• Levels of endometrial IGFBP-2 mRNA increased (p less than 0.05) between Days 10 and 18 of the estrous cycle and early pregnancy [13].

Anatomical context of IGFBP2

• The amount of IGFBP2 and IGFBP3 in follicular fluid increased [14].
• Percentage of total binding attributed to IGFBP-2 was greater (p < 0.05) in endometrium and serum ( approximately 30%) than in myometrium (16%) and uterine fluid (9%) [15].
• IGFBP-2, -3, -4, and -5 transcripts were observed in oviduct primary cultures throughout an 8-day interval [16].
• In situ hybridization indicated that IGFBP-1 mRNA was primarily localized in luminal epithelium of endometrium; IGFBP-2 mRNA was in luminal epithelium and dense stromal cells adjacent to endometrial epithelium; and IGFBP-3 mRNA was in vascular endothelial cells and was more prevalent in myometrium than in endometrium [15].
• At the doses tested, leptin and FSH had no effect (P > 0.10) on IGFBP-2, -3, -4, and -5 mRNA levels in large-follicle granulosa cells [17].

Associations of IGFBP2 with chemical compounds

• In experiment 2, E2 concentrations in large E-A follicles increased (p < 0.01) from 0 to 48 h after the PGF injection for control cows but decreased (p < 0.01) for FSH cows, whereas follicular fluid IGFBP-2 binding activity decreased from 0 to 48 h after PGF in controls and increased in FSH cows (treatment x time, p < 0.05) [18].
• Both IGFBP-2 and IGFBP-4 mRNA levels were consistently reduced in stretched cells but remained comparable to those of the control cells when the angiotensin II transducing pathway was blocked by inhibitors prior to the application of mechanical strain [19].
• Levels of IGFBP-2 and -5 mRNA were severalfold greater (P < 0.05) in subordinate than dominant follicles [20].
• Other features deduced from the bovine IGFBP-2 cDNA include: an abundance of leucine in the pre-peptide, an Arg-Gly-Asp sequence, absence of N-linked glycosylation sites, and an imperfect polyadenylation signal as well as an ATTTA motif in the 3' non-coding DNA [12].
• However, retinoic acid (10(-6) M) stimulated both IGFBP-2 and IGFBP-6 protein and mRNA levels, but it decreased IGFBP-3 mRNA levels relative to controls [21].

Physical interactions of IGFBP2

• IGF-II ligand blots confirm these tissue-specific differences in binding and show that each ocular tissue contains IGFBP-2 [22].

Regulatory relationships of IGFBP2

• Addition of IGF-I or -II to a control pool of bovine plasma did not significantly alter control IGF-binding protein-2 values in a radioimmunoassay [23].
• Thus, limit-feeding may reduce the effect of exogenous bST on growth rate by blunting bST-induced increases in IGF-I and IGFBP-3 and bST-induced decreases in IGFBP-2 [24].

Other interactions of IGFBP2

• In contrast, release of both IGFBP-2 and IGFBP-3 was greater (3.1-fold and 3.5-fold, respectively) from basal as compared to apical surfaces of the MDBKpMONBP-3 cells [25].
• Primary bovine mammary cells express the two IGF receptors (IGF-IR, IGF-IIR), insulin receptor, and four IGFBPs (IGFBP-2, -3, -4, and -5) [26].
• Intensities of the 34-kDa (IGFBP-2), 29-27-kDa, and 22-kDa IGFBP bands in follicular fluid were nondetectable or were lower (p < 0.01) in the fluid of large (> or = 8 mm) E-active (E-A; E2 > 50 ng/ml and > P4) follicles than in large E-inactive (E-I), medium (5-7 mm), or small (< 5 mm) follicles [18].
• Levels of GH receptor, the type 1 IGF receptor, and IGF binding protein-2 (IGFBP-2) mRNAs were unchanged across the growth-plate [27].
• The disappearance of binding activities for IGFBP-2 and smaller-molecular-mass IGFBPs in E-A follicles suggests a possible regulatory role for IGFBPs in follicular maturation and on aromatase activity.(ABSTRACT TRUNCATED AT 400 WORDS)[18]

Analytical, diagnostic and therapeutic context of IGFBP2

• Amounts of IGFBP-2, -3, -4, and -5 mRNA were quantitated using fluorescent quantitative real-time RT-PCR [17].
• Using specific antisera, immunoblotting showed that the 43,000 and 39,000 Mr bands were IGFBP-3 and the 34,000 Mr band was IGFBP-2 [28].
• Northern blot analysis of endometrial poly(A)+ RNA revealed two major transcripts of 7.5 and 1.0 Kb for IGF-I, one major transcript of 4.0 Kb for IGF-II, and one major transcript of 1.3 Kb for IGFBP-2 [13].
• Small follicles contained IGFBP-2, -3, -4, and -5 (determined by immunoprecipitation) [29].
• Media conditioned by MAC-T cells contained four forms of IGFBP that were identified, by western blotting with specific antibodies, as IGFBP-2, -3, -4 and -6 [21].

References