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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In neonatal rats, systemic administration of epidermal growth factor (EGF) results in reduced body weight gain and decreased levels of circulating IGF-I, which suggests that it be involved in the EGF-induced growth retardation. We investigated the effect of 4 weeks of EGF administration on circulating free and total IGF-I and IGF-binding proteins (IGFBPs) in adult rats treated with saline (controls), 30 (low dose group) and 150 (high dose group) microgram/kg/day EGF. Serum IGF-I was determined in ultrafiltrates (free) and acid-ethanol extracts (total), and serum IGFBPs using Western ligand blotting, which yielded four distinct molecular bands. The IGFBPs were tentatively identified as IGFBP-3 (a double band at 42 and 38 kDa), IGFBP-1 and/or IGFBP-2 (a single band at 30 kDa) and IGFBP-4 (a single band at 24 kDa). EGF administration did not change the body weight, tibia length, or liver, heart and lung weight. In contrast, serum total IGF-I and IGFBP-3 decreased dose-dependently: total IGF-I averaged 1470 +/- 100 micrograms/l (controls; mean +/- SEM), 1030 +/- 60 micrograms/l (low dose group; P < 0.005) and 760 +/- 40 micrograms/l (high dose group; P < 0.005), whereas differences between IGFBP-3 levels reached significance (P < 0.05) between controls and high dose rats, only. When compared to controls, levels of IGFBP-1 and/or IGFBP-2 were increased in the low dose group (P < 0.05), but unchanged in the high dose group. IGFBP-4 was unaffected by EGF. Free IGF-I averaged 74 +/- 6 micrograms/l in controls, and was reduced to 35 +/- 6 micrograms/l (low dose group; P < 0.005) and 57 +/- 5 micrograms/l (high dose group; P < 0.05). Free IGF-I was inversely correlated (r = -0.49, P < 0.05) with IGFBP-1 and/or IGFBP-2. We conclude that in adult rats prolonged EGF administration has a marked depressing effect on circulating total and free IGF-I. Nevertheless, we did not observe any somatic growth retardation.
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PMID:The effect of epidermal growth factor on circulating levels of free and total IGF-I and IGF-binding proteins in adult rats. 871 50

The objectives were to investigate whether insulin-dependent diabetes mellitus disrupts production of estradiol and activity of the insulin-like growth factor (IGF)-I system in individual ovarian follicles during the preovulatory period of the estrous cycle. Diabetes mellitus was induced with streptozocin (150 mg/kg) in seven cyclic gilts at 180 +/- 5 days of age. On Day 12 of the estrous cycle, insulin replacement therapy was withdrawn from three gilts and continued in four; four gilts served as normal controls. After ovary removal on Day 18, all follicles > or = 3 mm diameter were dissected free and cultured for 6 h in the presence of 280 ng testosterone for assessment of estradiol and IGF-I production and binding protein activity. Treatments did not affect corpora lutea number (15.4 +/- 0.8) or serum estradiol (5.8 +/- 0.8 pg/ml) on Day 18. There were no differences for any measure of follicular development between normal and insulin-treated diabetic gilts. Untreated diabetic gilts, compared to normal and insulin-treated diabetic gilts, had fewer total visible follicles (22.7 vs. 61.3 and 63.3; SEM = 8; p < 0.01) and reduced follicular diameter (3.4 vs. 4.4 and 4.2 mm; SEM = 0.3; p < 0.0001), respectively. Untreated diabetic gilts had a greater percentage of macroscopically atretic follicles than normal and insulin-treated diabetic gilts (75% vs. 47% and 36%; SEM = 10; p < 0.05). Untreated diabetes mellitus lowered estradiol (p < 0.01); however, effects of treatment on estradiol production were not significant when diameter was part of statistical models. When contents of IGF-I in follicular fluid and conditioned medium were summed after 6 h of culture, untreated diabetic pigs had lower IGF-I at all follicle diameters than pigs in the other treatments (p < 0.05). IGF binding protein (BP) activity was affected by diabetes mellitus, with untreated diabetic pigs having greater IGFBP-1 activity in medium and with both diabetic groups having greater IGFBP-2 activity in follicular fluid (p < 0.05). Activity of IGFBP-1 predominated in conditioned medium, and IGFBP-2 activity predominated in follicular fluid. 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). In conclusion, estradiol was most related to size of the follicle; however, lowering of IGF-I regardless of follicle diameter and alterations in IGFBP activity suggest that diabetes affects IGF-I and its binding proteins differently from estradiol production. These alterations may explain reduced follicular growth and increased follicular atresia in diabetic pigs.
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PMID:Depletion of insulin in streptozocin-induced-diabetic pigs alters estradiol, insulin-like growth factor (IGF)-I and IGF binding proteins in cultured ovarian follicles. 887 89

The aim of this study was to investigate the influence of hemodialysis on insulin-like growth factor-I (IGF-I) and the IGF binding proteins (IGFBPs) in patients with end-stage renal disease (ESRD). IGF-I and IGF-II circulate bound to IGFBPs which are known to influence the IGF-I bioavailability. Ten ESRD patients were studied before and after hemodialysis on low flux filters. IGF-I, insulin and IGFBP-I were measured by specific RIAs, and IGFBP-2 and IGFBP-3 were quantified by densitometry after Western ligand blotting. Diurnal curves of IGFBP-1 were performed in two additional patients. Before dialysis, the mean (+/- SEM) IGF-I level was 202.2 +/- 12.1 micrograms/l corresponding to a SD-score of 1.8 +/- 0.3. Basal IGFBP-1 was increased 2-fold compared to normal levels (82.4 +/- 24.1 micrograms/l) and increased further during hemodialysis to 118.1 +/- 28.5 micrograms/l (P < 0.007). The mean increase during dialysis in IGFBP-1 was 74 +/- 24%. Predialysis IGFBP-2 was increased to 184.8 +/- 32.5% of the reference serum and was not significantly changed by dialysis. The predialysis IGFBP-3, 38.5 kDa band was within normal levels 90.1 +/- 18.8% of the reference serum while the IGFBP-3, 41.5 kDa band was decreased to 62.4 +/- 11.3% of the reference serum. Both IGFBP-3 bands were not significantly changed after dialysis. The mean basal insulin level was high, 38.2 +/- 3.0 mU/L, in spite of normal glucose levels suggesting insulin resistance. The mean values of IGF-I, insulin and glucose were unchanged after dialysis. The ratio between IGF-I and IGFBP-1 decreased significantly after dialysis to 53% of the ratio before dialysis (P < 0.005). The ratio between IGF-I and IGFBP-2 or IGFBP-3 did not change after dialysis. The circadian variation of IGFBP-1 during dialysis days was impaired with a delayed decrease of IGFBP-1 compared to the non-dialysis day. In ESRD patients predialysis mean values of insulin, IGF-I SD-score, IGFBP-1 and IGFBP-2 were increased, while the mean densitrometric values of the IGFBP-3 bands on Western ligand blot were either normal or reduced. IGFBP-1 was raised significantly with a mean of 74% after dialysis, the predialysis level was more than 2-fold elevated with impaired circadian variation of IGFBP-1 on dialysis days. High levels of IGFBPs may bind free IGF-I and decrease IGF-I bioavailability thus contributing to the catabolism associated with dialysis.
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PMID:Decreased bioavailability of insulin-like growth factor-I, a cause of catabolism in hemodialysis patients? 889 46

Changes in insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBPs) were correlated with protein synthesis and breakdown using [1-13C]leucine before chemotherapy and during subsequent febrile neutropenia (FN) in eight children with cancer, aged 6.3-17.5 y. IGF-I levels were similar to age-matched controls before chemotherapy (mean +/- SEM: 250+/-28 and 228+/-22 microg l(-1), respectively). During FN, IGF-I fell to 156+/-22 microg l(-1) (p = 0.02), and rose to 276+/-27 microg l(-1) with recovery at 6 months (p = 0.004). Similarly, IGFBP-3 decreased from 4.0+/-0.2 mg l(-1) before chemotherapy to 3.0+/-0.3 mg l(-1) during FN (p = 0.01), and returned to 4.1+/-0.2 mg l(-1) at 6 months (p = 0.01). IGF-I correlated with IGFBP-3 (r = +0.7, p < 0.001). Scanning densitometry showed a decrease in IGFBP-3 from 94 to 54% during FN, when the presence of IGFBP-3 protease activity was observed. Compared with normal human serum, IGFBP-2 was elevated throughout the study. IGFBP-1 increased from 14.6+/-3.5 to 30.6+/-2.8 microg l(-1) (p = 0.004), whereas serum insulin decreased from 26.5+/-6.8 to 7.8+/-0.8 mU l(-1) (p = 0.03) before and during FN, respectively. Whilst IGF-I and IGFBP-3 fell, daytime growth hormone increased from 3.3+/-0.6 to 6.7+/-0.8 mU l(-1) (p=0.01), and cortisol from 197+/-48 to 594+/-98 nmol l(-1) (p = 0.005). Albumin decreased from 47+/-2 to 38+/-2 g l(-1) (p = 0.004) and improved to 47+/-2 g l(-1) with recovery (p = 0.003). Protein synthesis increased from 4.5+/-0.4 to 5.0+/-0.6 g kg(-1)d(-1) before chemotherapy and during FN, while protein breakdown rose from 5.4+/-0.4 to 6.3+/-0.4 kg(-1)d(-1). Increasing protein breakdown was related to falling IGF-I and IGFBP-3 levels. Modification of IGFBP-3 by circulating proteolytic activity may alter IGF bioavailability, allowing protein synthesis to increase during periods of severe catabolic stress.
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PMID:Changes in protein turnover, IGF-I and IGF binding proteins in children with cancer. 951 Apr 48

Non-islet cell tumour hypoglycaemia (NICTH) is characterised by severe and recurrent fasting hypoglycaemia, and is usually caused by secretion of insulin-like growth factor-II (IGF-II) by the tumour. This induces secondary changes in the circulating levels of insulin, growth hormone (GH), and the IGF-binding proteins (IGFBPs), resulting in an increased insulin-like hypoglycaemic activity of IGF-II. A participating role of IGF-I is not established. We measured serum levels of free IGF-I and free IGF-II, total IGF-I, total IGF-II, big IGF-II and IGFBP-1, IGFBP-2 and IGFBP-3 in patients with NICTH before (n=14) and after surgical removal of the tumour (n=3). A control group (n=20) was included for comparison. In NICTH patients, free IGF-II was 20-fold increased (26.8+/-8.1 [mean+/-SEM] vs. 1.3+/-0.1 microg/l), and free IGF-I was four fold increased (2.8+/-0.4 vs. 0.7+/-0.1 microg/l), as compared to control subjects (p < 0.0001). In accordance with earlier observations levels of total IGF-I, total IGF-II, and IGFBP-3 were decreased, whereas IGFBP-1 and IGFBP-2 were increased in NICTH (all p-values < 0.05). The highly elevated levels of free IGF-I and free IGF-II most likely imply a considerable hypoglycaemic insulin-like activity, and may, by negative feedback explain the marked suppression of the GH/IGF-I axis observed in NICTH. Finally, free IGF-II seems to be a powerful biochemical marker in the diagnosis of NICTH.
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PMID:Increased levels of circulating free insulin-like growth factors in patients with non-islet cell tumour hypoglycaemia. 962 78

Children with simple obesity (SO) show increased linear growth with normal or high serum insulin-like growth factor-I (IGF-I) levels during prepubertal period, despite low GH secretion. We measured IGF-I, IGFBP-1, GHBP and other factors to clarify the hormonal relation between the nutrition and the linear growth in SO and compared these factors with children with normal short stature (NS). Subjects were 23 SO and 19 NS children, and their height standard deviation (SD) scores were 0.7 +/- 0.2 SD and -3.4 +/- 0.3 SD (mean +/- SEM) (P < 0.01), respectively. Oral glucose tolerance test (OGTT) was performed in all the subjects and GH-releasing factor (GRF) test was also performed in 13 of SO and 17 of NS. The peak levels of GH in the GRF test were significantly lower in SO than in NS (12.8 +/- 1.7 vs. 39.8 +/- 6.9 ng/ml) and showed a significantly positive correlation with sigma IGFBP-1 (r = 0.63, P < 0.01). Serum GHBP level and IGF-I level were significantly higher in SO than in NS on pubertal stage matching. There was a positive correlation between GHBP and sigma insulin during OGTT (r = 0.75, P < 0.01). When the sum of the values during OGTT was expressed as sigma, sigma insulin, sigma C-peptide and sigma glucose were significantly higher in SO than in NS on pubertal stage matching. Basal and sigma IGFBP-1 were significantly lower in SO than in NS, but IGFBP-3 levels showed no significant difference between the two groups either in prepuberty or midpuberty. In conclusion, it can be hypothesized that the overnutrition causes hyperinsulinemia which increases GH receptor and IGF-I secretion despite low GH secretion. Hyperinsulinemia also may increase free IGF-I by lowering IGFBP-1. These two mechanism are supposed to be the nutrition related hormonal changes in SO and can explain the growth of SO. In addition, the increased free IGF-I may contribute the decreased GH secretion due to negative feedback in SO.
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PMID:Nutrition related hormonal changes in obese children. 970 Apr 75

IGFBP-1 is elevated in fetuses with long-term, chronic hypoxia and intrauterine growth restriction. We investigated the hypothesis that hypoxia regulates IGFBP-1 in the human fetus in vivo and IGFBP-1 gene expression and protein in vitro. Umbilical artery IGFBP-1 levels (mean +/- SEM) from term babies with respiratory acidosis (acute hypoxia), normal babies, and those with mixed respiratory/metabolic acidosis (more profound and prolonged hypoxia) were measured using an immunoradiometric assay. IGFBP-1 levels were similar in normal (n = 12) and acutely hypoxic (n = 6) babies (189.1 +/- 71.8 vs. 175.8 +/- 45.9 ng /ml, respectively, P = 0.789). However, with more profound and prolonged hypoxia (n = 19), IGFBP-1 levels were markedly elevated (470.6 +/- 80.0 ng /ml, P = 0.044). To investigate IGFBP-1 regulation by hypoxia in vitro, HepG2 cells were incubated under hypoxia (pO2 = 2%) and normoxia (pO2 = 20%). IGFBP-1 protein and mRNA increased 8- and 12-fold, respectively, under hypoxic conditions. Hypoxia did not affect protein or mRNA levels of IGFBP-2 or -4. IGFBP-5 and -6 mRNAs, undetectable in control cells, were not induced by hypoxia, whereas minimally expressed IGFBP-3 mRNA increased twofold. Investigation into IGFBP-1 gene structure revealed three potential consensus sequences for the hypoxia response element (HRE) in the first intron. To investigate functionality, a 372-bp fragment of IGFBP-1 intron 1, containing putative HREs, was placed 5' to a heterologous hsp70 promoter in a plasmid using luciferase as a reporter gene. Under hypoxia, reporter gene activity increased up to 30-fold. Mutations in the middle HRE abolished reporter activity in response to hypoxia, suggesting that this HRE is functional in the IGFBP-1 hypoxia response. Cotransfection of HRE reporter genes with a constitutively expressing hypoxia-inducible factor 1 plasmid in HepG2 cells resulted in a fourfold induction of reporter activity, suggesting a role for hypoxia-inducible factor 1 in hypoxia induction of IGFBP-1 gene expression. These data support the hypothesis that hypoxia regulation of IGFBP-1 may be a mechanism operating in the human fetus to restrict insulin-like growth factor-mediated growth in utero under conditions of chronic hypoxia and limited substrate availability.
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PMID:Hypoxia stimulates insulin-like growth factor binding protein 1 (IGFBP-1) gene expression in HepG2 cells: a possible model for IGFBP-1 expression in fetal hypoxia. 970 22

Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) gene transcription is known to be inhibited by insulin in vivo and in vitro. Levels of IGFBP-1 typically rise during fasting but also rise after acute hypoglycemia, including that induced by insulin, through an unknown mechanism that may involve counterregulatory hormones such as cortisol. To study the regulation of IGFBP-1 secretion during fasting, we measured IGFBP-1, insulin, cortisol, GH, and glucose during the course of standardized fasting studies in a total of 21 children. The fasting studies lasted 13-32 h and were terminated for a whole-blood glucose concentration of less than 50 mg/dL (2.8 mmol). Of the children studied, 9 children had no disorder, 8 had ketotic hypoglycemia, 2 had isolated GH deficiency, and 2 had fatty acid oxidation disorders. During fasting, IGFBP-1 rose above the mean baseline levels of 28+/-5 ng/mL to a mean level+/-SEM of 336+/-59 ng/mL at the time of hypoglycemia (P=0.001). IGFBP-1 was strongly associated with serum insulin and cortisol levels over the entire course of fasting (P < 0.0001)). The interaction of the 2 hormones across time was also strongly significant (P < 0.0001). There was no statistically significant association between IGFBP-1 and GH or glucose. At the time of hypoglycemia, insulin levels were suppressed to 1.7 microU/mL or less, and there was no correlation between IGFBP-1 levels at the end of fasting and final insulin level. In contrast, cortisol levels correlated with IGFBP-1 in the final hypoglycemic sample (r=0.56, P < 0.01). Partial correlation analysis revealed that the relationship between IGFBP-1 and cortisol was unchanged when the data was controlled for insulin levels. These data show that insulin and cortisol both regulate IGFBP-1 secretion during fasting; the effects of insulin and cortisol are strong during the course of fasting. Significant hypoglycemia stimulates a further rise in IGFBP-1, which seems to be regulated, in part, by cortisol. The cortisol-induced rise in IGFBP-1 during fasting and during hypoglycemia potentially serves to prevent the hypoglycemic effects of free IGFs.
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PMID:Dual regulation of insulin-like growth factor binding protein-1 levels by insulin and cortisol during fasting. 1037 46

An increasing series of pediatric endocrinopathies and metabolic anomalies has been recognized as related to reduced prenatal growth. We have tested whether the association of precocious pubarche (PP), dyslipidemia, and low serum IGF binding protein-1 in girls is also related to reduced prenatal growth. Fasting serum lipids, lipoproteins, and IGFBP-1 concentrations were measured in 187 girls (83 without PP and 104 with PP; mean age, 11.8 y; range, 5-18 y) with known birthweight and gestational age, the latter being transformed into birthweight SD scores. Birthweight SD scores of girls with PP were lower than those of girls without PP. Within the group of PP girls, those with dyslipidemia and low IGFBP-1 had lower (p < 0.0001) birth-weight SD scores (-2.02+/-0.23; mean +/- SEM) than those with normal lipids, lipoproteins, and IGFBP-1 (-0.37+/-0.15), whereas girls with an intermediate number of abnormalities had intermediate birthweight SD scores (-0.80+/-0.18). In conclusion, dyslipidemia and low serum IGFBP-1 in girls with PP were found to be related to reduced prenatal growth, an observation pointing to the prenatal origin of these metabolic abnormalities.
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PMID:Precocious pubarche, dyslipidemia, and low IGF binding protein-1 in girls: relation to reduced prenatal growth. 1047 48

Polycystic ovary syndrome (PCOS) is the most common cause of anovulation in women. Previous studies suggest that the pathogenesis of PCOS may involve interrelated abnormalities of the insulin-like growth factor (IGF) and ovarian steroidogenesis systems. We investigated this hypothesis in fasting serum samples from 140 women with PCOS (age, 27.4 +/- 0.4 yr; body mass index, 26.3 +/- 0.5 kg/m2; mean +/- SEM). IGF-related parameters were also studied in a group of normoovulatory women (n = 26; age, 26 +/- 4 yr; body mass index, 23.6 +/- 4.3 kg/m2). For the PCOS group, the mean testosterone (T) level was 2.5 +/- 0.1 nmol/L, and it was significantly correlated with LH (r = 0.41; P < 10(-6)), estrone (r = 0.33; P = 0.016), estradiol (r = 0.18; P = 0.04), and androstenedione (AD; P < 10(-6)), but not with dehydroepiandrosterone sulfate (P = 0.71), a marker of adrenal steroidogenesis. T and AD were also related to total ovarian follicle number and ovarian size, as previously found with normoovulatory women (1). There were no differences between the PCOS subjects and the normoovulatory group for total IGF-I, IGF-II, or IGF-binding protein-3 (IGFBP-3). However, IGFBP-1 levels were significantly decreased in the PCOS group (1.0 +/- 0.2 vs. 7.3 +/- 1.1 ng/mL; P < 0.001) and were inversely correlated with serum insulin levels (r = -0.50; P < 10(-8)). Serum levels of free IGF-I (fIGF-I) were elevated (5.9 +/- 0.3 vs. 2.7 +/- 0.3 ng/mL; P < 0.001) in inverse relation with IGFBP-1 (r = -0.31; P = 0.046). Serum fIGF-I levels were related to total follicle number (r = - 0.35; P < 10(-4)) and to the ratio of sex hormone-binding globulin to T (r = -0.23; P = 0.009). However, these relationships were not independent of other variables. Despite the more than 2-fold elevation in fIGF-I levels, significant relationships between fIGF-I and markers of ovarian steroidogenesis (T, AD, estradiol, and estrone) could not be demonstrated. In conclusion, although we confirmed correlations between LH and hyperandrogenemia and have found abnormalities in the IGF system in a large cohort of PCOS subjects, a direct relationship between hyperandrogenism and the IGF system could not be shown. Previous studies suggest that elevated LH and hyperinsulinemia lead to excess ovarian androgen synthesis in PCOS and that the intraovarian IGF system is important for normal follicle development and may be important in the arrested state of follicle development in PCOS. However, the data presented in this cross-sectional study suggest that insulin-related changes in circulating IGFBP-1 and subsequent elevation of fIGF-I reflect insulin resistance and have little enhancing effects on ovarian steroidogenesis in this disorder.
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PMID:Elevated serum levels of free insulin-like growth factor I in polycystic ovary syndrome. 1048 60


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