Disease relevance of IGFBP-3

• IUGR was associated with elevated plasma IGFBP-2 and IGFBP-4 and reduced IGFBP-3 levels [1].
• In contrast to findings in T47D breast cancer cells, treatment of PEMC cultures with IGFBP-3 did not result in increased levels of phosphosmad-2 [2].
• After 7 days of treatment, plasma IGFBP-3 concentrations and the plasma glucose response to a meal were also greater in pGH-treated than control pigs. pGH treatment significantly increased body weight gain and food conversion efficiency and the protein synthesis rate in several visceral organs [3].

Psychiatry related information on IGFBP-3

• These data have established that IGFBP-3 has the potential to affect proliferation of PEMCs during critical periods of muscle development that may impact ultimate muscle mass achievable postnatally [4].

High impact information on IGFBP-3

• Forskolin induced IGFBP-3 reporter activity in transiently transfected granulosa cells [5].
• We conclude that FSH stimulation of IGFBP-3 transcription is mediated by cAMP via the PKA pathway and requires the P1-3 kinase and likely the MAPK pathways [5].
• IGFBP-1, -2, -4, and -5 were of intermediate effectiveness as inhibitors, 3- to 11-fold less active than IGFBP-3 [6].
• One of these binding proteins, IGFBP-3, affects cell proliferation via both IGF-dependent and IGF-independent mechanisms and it has generally been shown to suppress proliferation of cultured cells; however, it also may stimulate proliferation depending upon the cell type and the assay conditions [7].
• Treatment of porcine embryonic myogenic cell (PEMC) cultures with either TGF-beta(1) or GDF-8 suppressed proliferation and increased production of IGFBP-3 protein and mRNA (P < 0.005) [2].

Biological context of IGFBP-3

• Currently, the effect, if any, of IGFBP-3 on myogenic cell proliferation is not known [4].
• In this study we show that embryonic porcine myogenic cells, unlike murine muscle cell lines, produce significant quantities of a binding protein immunologically identified as IGFBP-3 [8].
• CONCLUSION: These results indicate a coordinate gene expression of the IGF system in microembolised porcine myocardium, compatible with a role of IGF-I, IGFBP-3, IGFBP-5, and IGFBP-6 in inflammation-linked angiogenesis and/or repair processes [9].
• The two largest proteins were shown to be glycoproteins and immunologically related to porcine (p) IGFBP-3, suggesting that they are glycosylation variants of pIGFBP-3 [10].
• IGFBP-3 mRNA was not detected in developing follicles, but was detected in all luteal phase corpora lutea, apparently expressed by theca lutein cells [11].

Anatomical context of IGFBP-3

• IGFBP-3 reportedly may either suppress or stimulate proliferation of cultured cells depending on cell type [4].
• The follicular fluid (FF) level of IGFBP-3 did not differ significantly between healthy and atretic medium-sized (3- to 6-mm) follicles and was not significantly correlated with the percentage of granulosa cells containing hypodiploid levels of DNA (r = 0.181) or with endocrine parameters such as FF concentrations of estradiol or androstenedione [12].
• In situ hybridisation identified myocytes as the main producers of IGFBP-3 and IGFBP-6 mRNA [9].
• IGFBP-3 was decreased in follicular fluid of atretic follicles and in medium of atretic follicles in all except the insulin-treated diabetic gilts; in these gilts it was increased in atretic follicles (treatment by atresia interaction; p < 0.05) [13].
• IGFBP-3 and IGFBP-4 transcript levels became elevated in endometrium after implantation; whereas, IGFBP-5 and IGFBP-6 mRNAs were in greater abundance in periimplantation than post-implantation endometrium [14].

Associations of IGFBP-3 with chemical compounds

• The PEM isolated from sows fed L-carnitine had decreased IGF-II (P = 0.02), IGFBP-3 (P = 0.03), and myogenin (P = 0.04; 61, 59, and 67%, respectively) mRNA abundance compared with controls [15].
• IGFBP-4 is an inhibitor of basal progesterone, oxytocin and IGFBP-3 release and a stimulator of IGF-I output by porcine ovarian cells [16].
• It was observed that GH, IGF-I, estradiol, LH and oxytocin alter the progesterone, oxytocin, IGF-I and IGFBP-3 release by porcine ovarian granulosa cells [16].
• Dot-blot analyses for IGF-I and IGFBP-3 mRNAs were performed on total RNA from small and large luteal cells; blots were counter-probed with 3-phosphoglyceraldehyde dehydrogenase (p-GAD) cDNA to assess RNA quantity and quality [17].
• The present results suggested that IGFBP-4, as well as GH, IGF-I, estradiol, LH and oxytocin, is a potent regulator of porcine ovarian steroid (progesterone), nonapeptide hormone (oxytocin), growth factor (IGF-I) and growth factor-binding protein (IGFBP-3) release [16].

Regulatory relationships of IGFBP-3

• The simultaneous decrease in IGFBP-3 mRNA and protein that accompanies IGF-I-induced myogenin expression suggests that differentiation of myogenic cells may be preceded or accompanied by decreased production of IGFBP-3 [8].

Other interactions of IGFBP-3

• No treatment effect was found for muscle IGF-I (P = 0.36), IGF-II (P = 0.51), IGFBP-3 (P = 0.70), or IGFBP-5 (P = 0.51) mRNA abundance [15].
• Higher magnification revealed that IGF1R, IGFBP-3 and probably IGF-I appeared in the tubular system [18].
• An anti-IGFBP-3 antibody that neutralizes the biological activity of IGFBP-3 reduced the ability of either TGF-beta(1) or GDF-8 to suppress PEMC proliferation (P < 0.005) [2].
• In conclusion, the data point to IGF-I, IGF-II, IGFBP-2, and IGFBP-3 as putative mediators of relaxin-induced uterine growth in the pig [19].
• FFI IGFBP-3 was increased to a similar extent by GH (p < 0.005), but IGFBP-2 was not affected [20].

Analytical, diagnostic and therapeutic context of IGFBP-3

• Nonfusing cells subcultured from highly fused porcine myogenic cell cultures do not produce detectable IGFBP-3 protein or mRNA, thus suggesting the IGFBP-3 is produced by muscle cells in the porcine myogenic cell cultures [8].
• Northern blots showed readily detectable transcripts for IGF-I (6.7 and 0.9 kb), IGFBP-2 (1.8 kb), IGFBP-3 (2.8 kb), IGFBP-4 (2.6 kb), and IGFBP-5 (6.0 kb), but not for IGFBP-6 [17].
• The secretion of IGF-I, OT, IGFBP-3, progesterone and PGE was determined using RIA/IRMA, whilst the IGF-I binding sites were measured using a radioreceptor assay [21].
• Plasma IGF-I concentration was measured by radioimmunoassay and plasma IGFBP-3 and IGFBP-2 were estimated by Western ligand blotting [22].
• The two major forms of circulating IGFBP, as estimated by Western blot analysis, were identified putatively as IGFBP-2 and IGFBP-3 (relative molecular weights of 34 and 40-45 kDa respectively) [23].

References