Disease relevance of IGF1

• This study was designed to determine the potential of IGF-1 as a neuronal rescue agent after cerebral ischemia [1].
• Decreased serum insulin-like growth factor-I associated with growth failure in newborn lambs with experimental cyanotic heart disease [2].
• Insulin-like growth factor (IGF-1) markedly increases myelination and glial numbers in white matter after ischemia in near-term fetal sheep; however, it is unclear whether this is due to reduced cell loss or increased secondary proliferation [3].
• In conclusion, IGF-1 can prevent delayed, postischemic oligodendrocyte cell loss and associated demyelination [4].
• IUGR fetuses received daily intraamniotic injections of saline or IGF-1 (20 microg/d) from 120 to 130 days [5].

High impact information on IGF1

• Developmental patterns of insulin-like growth factor-I and -II synthesis and regulation in rat fibroblasts [6].
• Overexpression of ovine insulin-like growth factor-I stimulates autonomous autocrine or paracrine growth in bovine mammary-derived epithelial cells [7].
• The circulating molecular weight forms of infused recombinant insulin-like growth factor-I and effects on glucose and fat metabolism in lambs [8].
• Ninety minutes after the occlusion, fetuses were given, intracerebroventricularly, either a single dose of IGF-1 (either 3 or 30 micro g), or 3 micro g followed by 3 micro g over 24 hours (3 + 3 micro g) [3].
• Thus, increased oligodendrocyte numbers after IGF-1 treatment is partly due to suppression of apoptosis, and partly to increased proliferation [3].

Biological context of IGF1

• Alternative splicing of ovine insulin-like growth factor-I (IGF-I) transcripts generates three different mRNAs [9].
• Characterization of multiple transcription initiation sites of the ovine insulin-like growth factor-I gene and expression profiles of three alternatively spliced transcripts [9].
• A BglII RFLP at the ovine locus for insulin-like growth factor 1 (IGF1) [10].
• Circulating IGF-1 may in part mediate the regulation of fetal growth in response to fetal nutrient supply [11].
• In contrast, expression of IGF-1 mRNA was low (compared to estrous levels) and ubiquitous decreasing as gestation advanced [12].

Anatomical context of IGF1

• Insulin-like growth factor-1 (IGF-1) is known to be important for oligodendrocyte survival and myelination [4].
• Levels of insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding proteins (IGFBPs) were studied in ovine follicular fluid and serum with a view to determining their respective endocrine and/or paracrine roles in ovarian folliculogenesis [13].
• Localization of insulin-like growth factor-I (IGF-I) and -II messenger ribonucleic acid and type 1 IGF receptors in the ovine uterus during the estrous cycle and early pregnancy [14].
• Changes in insulin-like growth factor-I (IGF-I), IGF-II, and their binding proteins during growth and atresia of ovine ovarian follicles [13].
• Control of growth hormone receptor and insulin-like growth factor-I expression by cortisol in ovine fetal skeletal muscle [15].

Associations of IGF1 with chemical compounds

• Secretion of progesterone by CL of 88-90 days of pregnancy was not affected by IGF1, IGF2, PAF-16, PAF-18, oxytocin, PGI2, PGD2 or leukotriene C4 (P > or = 0.05) [16].
• Twice-weekly blood samples were collected to monitor long-term changes in the blood concentrations of: (1) pituitary; (2) metabolic; and (3) reproductive hormones (prolactin, GH, alpha-MSH, beta-endorphin, ACTH, TSH, LH, FSH, cortisol, insulin, IGF1 and testosterone) [17].
• We have investigated the relationship between the plasma distribution of infused recombinant insulin-like growth factor-I across the insulin-like growth factor binding proteins and the resultant effects on glucose and fat metabolism [8].
• Synergistic effect of insulin-like growth factor-I administration on the protein-sparing effects of total parenteral nutrition in fasted lambs [18].
• Regulation of insulin-like growth factor-I and progesterone synthesis by insulin and growth hormone in the ovine ovary [19].

Regulatory relationships of IGF1

• Growth hormone and amino acid supply interact synergistically to control insulin-like growth factor-I production and gene expression in cultured ovine hepatocytes [20].
• IGF-1 stimulates the IGF-1 receptor (IGF1R) and downstream signaling pathways, including extracellular signal-regulated kinase (ERK) and phosphoinositol-3 kinase (PI3K) [21].

Other interactions of IGF1

• Sheep gene mapping: additional DNA markers included (CASB, CASK, LALBA, IGF-1 and AMH) [22].
• At necropsy on day 78 or day 135 of gestation, gravid uteri were recovered. mRNA expression of IGF-1 and IGF-2 in ventricles were measured with RT-PCR, and protein expression of IGF-1R, IGF-2R, IGFBP-3 was quantitated with Western blot [23].
• Regulation of gelatinase-A (MMP-2) production by ovine intervertebral disc nucleus pulposus cells grown in alginate bead culture by Transforming Growth Factor-beta(1)and insulin like growth factor-I [24].
• IGF-1 treatment was associated with reduced caspase-3 activation and increased glial proliferation in a similar dose-dependent manner [3].
• The effects of cortisol on hepatic GH receptor and insulin-like growth factor-I (IGF-I) gene expression were investigated in sheep fetuses during late gestation and after experimental manipulation of plasma cortisol levels by fetal adrenalectomy and exogenous infusion of cortisol [25].

Analytical, diagnostic and therapeutic context of IGF1

• Five transgenic lambs resulted from the microinjection of 591 embryos; one male and one female showed IGF1 expression in the skin [26].
• Passive immunization against insulin-like growth factor-I does not inhibit growth hormone-stimulated growth of dwarf rats [27].
• Intravenous infusions of amino terminal methionyl insulin-like growth factor-I (N-Met IGF-I; 8 micrograms/kg body wt x h; 24 h) were performed in lactating sheep and samples of mammary lymph, cerebrospinal fluid, and postinfusion tissues collected to examine distribution of the recombinant analog outside the vascular space [28].
• Insulin-like growth factor-I (IGF-I), IGF-II, and the type 1 IGF receptor (IGF-IR) gene transcripts were localized in sections of ovine uterus collected from 53 ewes at different stages during the estrous cycle and the first 3 weeks of pregnancy using in situ hybridization with synthetic oligonucleotides [14].
• Comparative plasma IGF-1 concentrations determined by the method correlated closely (P less than 0.001) with corresponding values where BPs were removed by acid gel filtration [29].

References