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

• Fetal hepatic IGF-I, IGFBP-2, -3 and -4 concentrations rose over gestation (p < 0.05), but there were no treatment effects [8].
• The deduced amino acid sequence of the ovine IGFBP-2 showed 86, 95 and 85% homology with the rat, bovine and human peptide sequences respectively [9].
• In later gestational ages and early postnatal life, when IGF-II mRNAs were expressed in decreasing levels, IGFBP-2 mRNA was present only in selected tissues [10].
• 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 [11].
• The different affinities of des(1-3)IGF-I for IGFBP-3, -2, and -1 lead us to suggest that IGFBP-2 and/or -1 are present in the deep stroma and glands, whereas IGFBP-3 may be responsible for the additional binding sites in the myometrium and blood vessel walls [12].

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

• IGFBP-2 was suppressed (P less than 0.05) by day 55 and IGFBP-3 and 4 did not change [20].
• Growth hormone stimulates the secretion of insulin-like growth factor binding protein-2 (IGFBP-2) by monolayer cultures of sheep costal growth plate chondrocytes [21].

Other interactions of IGFBP-2

• As revealed by Western ligand and immunoblotting, OACs secreted IGFBP-2 and a 24-kDa IGFBP in culture medium under basal conditions [22].
• In vitro, IGFBP-2 and particularly IGFBP-5 were the main IGFBPs secreted by ovine granulosa cells [7].
• Type 1 IGF receptor expression was increased (P < 0. 01) in the luminal epithelium of the HM group and IGFBP-2 mRNA expression was highest in the placentome capsule of ewes in the HH group [23].

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].

References