Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We performed a double-blind randomized placebo-controlled trial of recombinant human growth hormone (hGH) in normally lactating women (N = 8 per group) to investigate the endocrine mode of action of the galactopoietic effect of this hormone. Insulin-like growth factors I (IGF-I) and II (IGF-II) and their binding proteins (IGFBP-1, IGFBP-2 and IGFBP-3) were measured by radioimmunoassay in plasma and milk samples collected throughout the study. All assays were validated for human plasma and milk. Human GH treatment (0.1 IU.kg-1 body wt.day-1 for 7 days) increased plasma concentrations of IGF-I from 22.1 +/- 1.3 nmol/l (mean +/- SEM) to 59.7 +/- 2.5 nmol/l (p < 0.01). At the end of the study the increase in plasma IGF-I correlated significantly with the increase in milk volume (r = 0.67, p < 0.005, N = 16). The IGF-I levels were considerably lower in milk, with 0.14 +/- 0.03 nmol/l before and 0.31 +/- 0.04 nmol/l after hGH treatment. The increase in milk IGF-I levels (134.0 +/- 14.5%) with hGH treatment was significant (p < 0.01) and plasma and milk IGF-I concentrations correlated significantly when considering all samples of the study (r = 0.45, p < 0.001, N = 56). The concentrations of IGF-II were not changed significantly with hGH treatment in plasma (52.5 +/- 2.5 nmol/l before and 42.6 +/- 3.9 nmol/l after treatment) or milk (2.1 +/- 0.29 nmol/l before and 2.3 +/- 0.49 nmol/l after hGH treatment).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin-like growth factors and their binding proteins in plasma and milk after growth hormone-stimulated galactopoiesis in normally lactating women. 750 71

Insulin-like growth factor binding proteins 1 and 3 are essentially known as regulators of IGF bioactivity. However, we previously showed that IGFBP-3 was able, in chick embryo fibroblast (CEF), to 100% inhibit DNA synthesis stimulated by calf serum, while the maximal inhibition found with IGFBP-1 was 60%, suggesting a difference between the two IGFBPs in their biological functions. Results of the present work agree with this assumption: (a) Recombinant human IGFBP-3, like rat IGFBP-3, was able to 100% inhibit DNA synthesis stimulation induced by human serum, while this stimulation was 75% decreased by IGFBP-1. However, the most striking difference was observed when the effects of the two IGFBPs were compared for stimulation induced by a serum growth factor (SGF) fraction depleted in IGFs. Stimulation induced by the SFG fraction was more significantly decreased (p < 0.001) by IGFBP-3 than by IGFBP-1. The mean percent inhibition +/- SEM was 67.1 +/- 2.5 in the presence of IGFBP-3 (200 ng/ml) and 29.3 +/- 2.7 and 34.2 +/- 4 in the presence of 200 and 400 ng/ml IGFBP-1 respectively. Inhibition by 200 ng/ml IGFBP-1 and inhibition by 6 ng/ml IGFBP-3 were additive. However, inhibition by IGFBP-3 and that by IGFBP-1 were no longer additive at high concentrations of IGFBP-3, which might thus replace IGFBP-1. (b) FGF stimulation of CEF was similarly inhibition (65% and 70%) by IGFBP-1 and IGFBP-3. (c) TGF beta stimulation of CEF was more strongly decreased by IGFBP-3 (90%) than by IGFB-1 (60%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Difference in biological effects between insulin-like growth factor binding protein 1 and 3. 752 Jul 13

We describe a case of recurrent hypoglycaemia associated with a hepatoma. During hypoglycaemia serum insulin was undetectable. Plasma insulin-like growth factor II (IGF-II) was not elevated although 71% of plasma IGF-II was present as big IGF-II (molecular weight 11 kDa) which probably represents a non-glycated form of pro-IGF-II. The GH response to hypoglycaemia was impaired and plasma levels of both IGF-I and the GH-dependent IGF binding protein (IGFBP-3) were low. A recently described unextracted assay directed against the first 21 amino acids of the E-domain (E-21) of proinsulin-like growth factor-II (pro-IGF-II) allows direct plasma estimation (plasma E-21) of larger molecular forms of IGF-II without interference from normal IGF-II and IGF binding proteins. Basal values were grossly elevated (23.7 and 23.8 nmol/l). Treatment with GH led to an increase in the mean plasma glucose across 24 hours (4.25 +/- 0.21 mol/l (mean +/- SEM) before treatment, compared with 4.86 mmol/l +/- 0.17 following GH (P < 0.01)) and a reduction in hypoglycaemic attacks. The treatment was associated with a rise in IGFBP-3 and small increases in insulin like growth factors. Subsequent treatment with the somatostatin analogue octreotide did not produce a significant change in plasma glucose levels or insulin-like growth factors. Two courses of intrahepatic adriamycin restored elevated levels of E-21 to normal. Total IGF-II remained normal and IGF-I increased. GH treatment was successfully withdrawn with no effect on plasma glucose or growth factor levels. The patient remained free from hypoglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A case of hepatoma associated with hypoglycaemia and overproduction of IGF-II (E-21): beneficial effects of treatment with growth hormone and intrahepatic adriamycin. 752 21

Serum concentrations of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3), the carboxyterminal propeptide of type I collagen (PICP), the carboxyterminal pyridinoline crosslinked telopeptide of type I collagen (ICTP), and the aminoterminal propeptide of type III procollagen (PIIINP) were studied in 10 prepubertal children with asthma (mean age 9.0 years). The children were treated with 2.5 and 5.0 mg/day prednisolone in a randomised double blind crossover trial with run in, treatment, and washout periods of two weeks. No statistically significant effects on serum concentrations of IGF-I and IGFBP-3 were found. Dose related reductions of PICP, ICTP, and PIIINP were observed: the mean (SEM) reduction in PICP was 33.4 (26.3) and 68.4 (20.6) micrograms/l, in ICTP 2.5 (0.5) and 2.9 (0.6) micrograms/l, and in PIIINP 2.1 (0.7) and 3.1 (1.8) micrograms/l during the 2.5 and 5.0 mg prednisolone periods respectively. Short term treatment with low daily doses of prednisolone is associated with suppression of serum markers of type I and III collagen turnover in children with asthma. Intermediate and long term effects remain to be studied.
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PMID:The insulin-like growth factor axis and collagen turnover during prednisolone treatment. 752 81

The liver is thought to be the major source of circulating insulin-like growth factor (IGF-I) and IGF-binding protein-1 (IGFBP-1), whereas the primary production site of circulating IGFBP-3 remains unknown. As other tissues may contribute to the circulating pool of IGF-I and IGFBP, the aim of the present study was to assess the hepatic and renal arterio-venous difference and production rates of IGF-I, IGFBP-1, IGFBP-3, and GH in cirrhotic patients (n = 22) and matched control subjects (n = 27). IGFBP-1 and -3, IGF-I, and GH levels were measured by RIA in hepatic, renal, and peripheral veins and in the femoral artery. Levels of IGFBP-1 to -4 were additionally determined by Western ligand blotting. Hepatic venous IGFBP-1 was significantly increased in the cirrhotic patients (mean +/- SEM, 33.6 +/- 9.1 vs. 10.4 +/- 1.9 micrograms/L; P < 0.001), and arterio-renal-venous extraction was significant in both patients (6 +/- 2%; P < 0.01) and controls (11 +/- 1%; P < 0.001). Conversely, IGFBP-3 was decreased in the cirrhotic patients (1265 +/- 149 vs. 2712 +/- 137 micrograms/L; P < 0.001). IGFBP-3 correlated significantly with the wedged hepatic venous pressure (r = -0.49; P < 0.05), serum aspartate aminotransferase (r = -0.66; P < 0.01), serum bilirubin (r = -0.65; P < 0.01), serum albumin (r = 0.64; P < 0.01), and the Child score (r = -0.57; P < 0.01). IGF-I was significantly lower in the cirrhotics (57 +/- 10 vs. 143 +/- 11 micrograms/L; P < 0.001). No significant IGFBP-3 proteolysis was demonstrated in cirrhotics or controls. No significant differences were found in the values obtained simultaneously from hepatic, renal, and brachial veins or femoral artery, which suggests that no major net production or release of IGFBP-3 or IGF-I occurs in these tissues. No differences in IGFBP-2 or IGFBP-4 determined by Western ligan blot were found between patients and controls. The IGF-I concentrations correlated significantly with parameters of biochemical liver function. Basal GH concentrations were significantly higher in the cirrhotics (1.19 +/- 0.13 vs. 0.58 +/- 0.08 micrograms/L; P < 0.001). A significant hepatic disposal of GH was found in the patients (P < 0.05) and controls (P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Concentrations, release, and disposal of insulin-like growth factor (IGF)-binding proteins (IGFBP), IGF-I, and growth hormone in different vascular beds in patients with cirrhosis. 753

The purpose of this study was to determine the effects of recombinant human GH (rhGH; 0.025 mg/kg.day) and one of two doses of recombinant human insulin-like growth factor-I (rhIGF-I; 0.015 and 0.060 mg/kg, twice daily) on body composition in elderly women. Sixteen healthy elderly women (mean age +/- SEM, 71.9 +/- 1.3 yr) were randomly assigned to receive either rhGH (GH; n = 5), low dose rhIGF-I (n = 6), or high dose rhIGF-I (n = 5). A 2-week predrug baseline period was followed by 4 weeks of hormone treatment, with a standardized diet fed throughout. All groups experienced a significant increase in serum IGF-I and IGFBP-3 levels over the treatment period, accompanied by significant decreases in IGF-II (P < 0.05). Fat mass decreased in all groups, with significant increases in lean body mass and nitrogen retention occurring in the high dose IGF and GH groups. Total body water did not change, whereas increases observed in intracellular fluid approached significance (P = 0.06). These anabolic changes were accompanied by numerous negative side-effects in the GH and high dose IGF groups, including headaches, lethargy, joint swelling/pain, and bloatedness. The low IGF dose was well tolerated. These results demonstrate that the administration of rhGH and rhIGF-I for 4 weeks results in anabolic changes in body composition in elderly women.
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PMID:The effects of recombinant human insulin-like growth factor-I and growth hormone on body composition in elderly women. 753 17

Obesity is associated with suppressed growth hormone (GH) concentrations but relatively little is known about insulin-like growth factors(IGFs) and binding proteins for GH and IGFs (GHBP and IGFBPs) and the modulatory effect of GH administration. In a double-blind, crossover design we studied the impact of 5 weeks of placebo or GH administration (0.03 mg.kg-1 body wt.day-1) in nine obese women (mean +/- SEM: age 30.4 +/- 2.4 years; body mass index 37.0 +/- 2.8 kg/m2) on IGF-I, IGF-II, IGFBP-1 and -3 and GHBP. Serum IGF-I (microgram/l) levels were subnormal and increased significantly following GH (117 +/- 16 (placebo) vs 434 +/- 33 (GH) vs 198 +/- 15 (control (p < 0.01)). By contrast, serum IGF-II (microgram/l) levels were in the normal range and remained unchanged (608 +/- 20 (placebo) vs 647 +/- 40 (GH) (NS)). Serum IGFBP-3 was in the normal range and increased significantly during GH treatment, although relatively less than IGF-I, such that the molar ratio between IGF-I and IGFBP-3 increased with GH treatment, whereas the ratio between IGF-I + IGF-II and IGFBP-3 remained unchanged. Serum IGFBP-1 was low in the placebo situation but became further and almost completely suppressed during GH treatment. During a 2-h hyperinsulinemic, euglycemic glucose clamp, IGFBP-1 decreased in the placebo study and remained suppressed during GH. Serum GHBP (nmol/l) levels were elevated substantially compared to non-obese controls (p < 0.001) and did not change during GH treatment (2.37 +/- 0.36 (placebo) vs 2.21 +/- 0.25 (GH) vs 0.80 +/- 0.19 (control)).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum concentrations of insulin-like growth factors (IGFs), IGF binding proteins 1 and 3 and growth hormone binding protein in obese women and the effects of growth hormone administration: a double-blind, placebo-controlled study. 754 82

Endogenous GH secretion is pulsatile. Animal studies indicate that GH administered in a pulsatile manner induces growth and insulin-like growth factor I (IGF-I) generation more effectively than continuous administration. Short term human studies, however, have reported similar metabolic effects with constant and pulsatile GH delivery. This study was carried out to compare the metabolic effects of longer term continuous infusion vs. daily injections of GH. Thirteen GH-deficient patients were studied in a cross-over design. The patients were randomized to receive GH as a continuous sc infusion by means of a portable pump for 1 month and as daily sc injections (at 1900 h) for another month. An average daily GH dosage (+/- SEM) of 3.15 +/- 0.27 IU was administered during both periods. Steady state 24-h profiles of GH, IGF-I, IGF-binding proteins (IGFBPs), insulin, glucose, lipid intermediates, and other metabolites were monitored after each treatment period. At the end of each study period (at 0800 h), an oral glucose tolerance test was performed. The mean (+/- SEM) integrated levels of serum GH (micrograms per L) were higher after GH injection [2.51 +/- 0.54 (injection) vs. 1.77 +/- 0.35 (infusion); P < 0.02]. Continuous infusion induced higher nighttime than daytime GH levels (P = 0.01), indicating a diurnal variation in the absorption or clearance of GH. Serum IGF-I levels (micrograms per L) were slightly higher (P < 0.05, by analysis of variance) after continuous GH infusion [312.5 +/- 50.2 (injection) and 334.6 +/- 46.6 (infusion)]. Similarly, constant GH delivery induced higher IGFBP-3 levels (P < 0.05, by analysis of variance). Serum IGFBP-1 levels were similar on the two occasions. Daily GH injections increased daytime insulin levels (P < 0.05), whereas 24-h levels were similar (P = 0.14). The trend toward increased insulin levels after GH injections was also found during the oral glucose tolerance test (P = 0.07). Blood glucose levels were identical on the two occasions. Nocturnal levels of nonesterified fatty acids were higher (P < 0.05) after GH injection. We conclude that continuous sc infusion of GH induced serum IGF-I and IGFBP-3 levels more effectively than daily sc injections. The constant appearance of GH in the circulation did not impair glucose tolerance, but resulted in a less physiological diurnal pattern of nonesterified fatty acids. Our data do not support the concept that a pulsatile GH pattern is of critical physiological significance.
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PMID:Continuous infusion versus daily injections of growth hormone (GH) for 4 weeks in GH-deficient patients. 754 14

To study the possible role of insulin-like growth factor binding proteins (IGFBPs) in the discrepancy between normal or only slightly retarded growth and substantially reduced concentrations of insulin-like growth factor I (IGF-I) in prepubertal children with insulin-dependent diabetes mellitus (IDDM), we measured the plasma concentrations of IGF-I, IGFBP-1, IGFBP-2 and IGFBP-3 and free insulin in 24 prepubertal diabetic subjects and 12 control children. In addition, the growth hormone response to exercise was evaluated. The diabetic children had significantly decreased peripheral IGF-I levels (8.2 + 1.1 (SEM) vs 16.7 + 2.5 nmol/l; p < 0.001), whereas the concentrations of free insulin were increased (217 + 14 vs 103 + 21 pmol/l; p < 0.001). The concentrations of IGFBP-1 and IGFBP-3 were of the same magnitude in both groups. The diabetic children had significantly increased levels of IGFBP-2 (465 + 13 vs 416 + 14 micrograms/l; p = 0.029), which were inversely related to the circulating IGF-I levels (r = -0.35; p = 0.034). The diabetic and control children had comparable growth hormone responses to exercise. Diabetic children with poor glucose control had even lower IGF-I levels than those with moderate metabolic control (6.0 + 0.8 vs 10.3 + 1.7 nmol/l; p = 0.037). No differences could be observed in the plasma concentrations of various IGFBPs between these two groups of diabetic subjects. The absence in prepubertal diabetic children of increased IGFBP-1 levels observed in adolescent and adult patients with IDDM may contribute to their maintained linear growth, despite definitely decreased IGF-I concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin-like growth factor binding proteins in prepubertal children with insulin-dependent diabetes mellitus. 758 67

The resting metabolic rate (RMR), and body composition were assessed in 30 growth hormone-deficient (GHD) adults before and after 3 and 6 months of replacement therapy with recombinant human growth hormone (rhGH). In addition, insulin-like growth factor I (IGF-I), IGF binding proteins (IGFBPs) and plasma insulin were measured at baseline and at 6 months in relation to RMR. During 6 months of rhGH replacement therapy, body fat decreased from 18.2 +/- 1.5 (mean +/- SEM) to 14.3 +/- 1.6 kg (p < 0.0001), whereas fat-free mass (FFM) increased from 53.5 +/- 3.3 to 56.3 +/- 3.6 kg (p < 0.0001), RMR increased from 1246 +/- 92 to 1539 +/- 102 kcal/24 h (p < 0.0001) and RMR per kilogram of FFM increased from 23.2 +/- 0.6 to 27.4 +/- 0.5 (p < 0.0001). When RMR data were adjusted for the differences in FFM, it appeared that apart from the increase in FFM, other factors may play a role in the increase in RMR. During rhGH replacement therapy, IGF-I (p < 0.0001) and IGFBP-3 (p = 0.003) levels increased, whereas IGFBP-1 levels decreased significantly (p = 0.004). The FFM explained for about 80% of the variance in RMR. In addition, waist/hip ratio and plasma IGF-I contributed significantly to the explained variance of RMR. This study shows that in GHD adults FFM is the main determinant of RMR and that, next to the increase in FFM, changes in metabolic and hormonal parameters contribute to the increase in RMR during rhGH replacement therapy.
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PMID:Resting metabolic rate, body composition and related hormonal parameters in growth hormone-deficient adults before and after growth hormone replacement therapy. 758 68


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