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

The effect of recombinant GH on strength, body composition and endocrine parameters in power athletes was investigated in a controlled study. Twenty-two healthy, non-obese males (age 23.4 +/- 0.5 years; ideal body weight 122 +/- 3.1%, body fat 10.1 +/- 1.0%; mean +/- SEM) were included. Probands were assigned in a double-blind manner to either GH treatment (0.09U (kg BW)-1 day-1 sc) or placebo for a period of six weeks. To exclude concurrent treatment with androgenic-anabolic steroids urine specimens were tested at regular intervals for these substances. Serum was assayed for GH, IGF-I, IGF-binding proteins, insulin and thyroxine before the onset of the study and at two-weekly intervals thereafter. Maximal voluntary strength of the biceps and quadriceps muscles was measured on a strength training apparatus. Fat mass and lean body mass were derived from measurements of skinfolds at ten sites with a caliper. For final evaluation only data of those 8 and 10 subjects in the two groups who completed the study were analyzed. GH, IGF-I and IGF-binding protein were in the normal range before therapy and increased significantly in the GH-treated group. Fasting insulin concentrations increased insignificantly and thyroxine levels decreased significantly in the GH-treated probands. There was no effect of GH treatment on maximal strength during concentric contraction of the biceps and quadriceps muscles. Body weight and body fat were not changed significantly during treatment. We conclude that the anabolic, lipolytic effect of GH therapy in adults depends on the degree of fat mass and GH deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes. 768 51

Insulin-like growth factor (IGF) I has important growth regulatory functions in normal growth and development. IGF-I is also a mitogen for a number of cancer cell lines; however, its autocrine effect has not been well established. In this study, the expression of IGF-I, its receptor, and its major serum-binding protein were examined in 5 normal human mesothelial (NHM) cell samples and 11 pleural mesothelioma cell lines. All NHM cells and mesothelioma cell lines expressed IGF-I, IGF-binding protein 3 (IGFBP-3), and IGF-I receptor mRNA by either Northern blot or reverse transcription polymerase chain reaction analysis. IGF-I (0.136 +/- 0.024 ng/ml, mean +/- SEM) and IGFBP-3 (18.5 +/- 3.2 ng/ml) proteins were readily detected in the conditioned medium of mesothelioma cell lines but were not greater than corresponding measurements in that of NHM cells (IGF-I, 0.120 +/- 0.080 ng/ml; IGFBP-3, 15.9 +/- 1.3 ng/ml). Exogenous recombinant IGF-I stimulated cell proliferation of NHM cells, demonstrating the presence of a functional IGF-I receptor. Our results suggest that IGF-I may function as an autocrine growth stimulus in normal proliferating mesothelial cells, which may contribute to their malignant transformation.
 ...
PMID:Normal human mesothelial cells and mesothelioma cell lines express insulin-like growth factor I and associated molecules. 768 50

A radioimmunoassay (RIA) for the rat growth hormone binding protein (GHBP) was developed using a synthetic peptide (corresponding to the hydrophilic carboxyl-terminal sequence of mouse GHBP) as standard and a monoclonal antibody (MAb 4.3) reactive with this peptide as the primary antibody. The values for GHBP concentration obtained for normal rats using this assay compare favourably with those obtained by gel filtration and ELISA methods. The concentration of GHBP in normal male rats at 11 weeks of age (680 +/- 30 ng/ml, SEM, n = 9) was significantly less than the concentration in normal females (943 +/- 47 ng/ml, SEM, n = 25). In 11-week-old dwarf male rats the concentration of GHBP was 423 +/- 35 ng/ml (n = 8); less than in dwarf females (542 +/- 32, P < 0.05, n = 9) and normal males (680 +/- 30, P < 0.001, n = 9). The GHBP concentration in dwarf rats was not age-dependent, whereas in normal females the concentration of GHBP increased with age. The availability of an RIA which is not susceptible to interference by endogenous GH, will facilitate further studies on hormonal and nutritional regulation of the rat GHBP. The assay was applied to studying the effects of IGF-I infusion (240 micrograms/day for 1 week) and GH injection (65 micrograms/100 g body weight, twice daily for 1 week and 4 weeks) on the serum concentration of GHBP in 11-week-old Lewis dwarf rats. Hepatic GH binding sites were also measured in desaturated membranes from the same animals.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serum growth hormone binding protein and hepatic GH binding sites in the Lewis dwarf rat: effects of IGF-I and GH. 775 72

To assess the possible role of placental growth hormone (GH) in fetoplacental growth, we measured placental and pituitary GH (GHN) in maternal plasma by means of two RIA using two MAb (5B4 recognizing both placental GH and GHN, and K24 recognizing only GHN) during pregnancy. IGF-I also was measured by RIA in the same samples after extraction. A transverse study of 186 samples obtained between 8 wk of amenorrhea (WA) and term confirmed the reported rise in GH immunoreactivity with 5B4 after 24 to 25 WA from 12.3 +/- 2.0 mU/L (mean +/- SEM) to a plateau of 27.5 +/- 3.4 mU/L at 34 to 35 WA together with the decrease in GHN to undetectable levels by 24 to 25 WA. IGF-I levels increased from 164.0 +/- 44.6 micrograms/L at 24 to 25 WA to 331.6 +/- 63.6 micrograms/L at term. A longitudinal study of 31 normal pregnant women confirmed this hormonal pattern and the reported placental GH plateau after 35 WA. A drastic decrease in placental GH was observed with the onset of labor (from 26.9 +/- 2.1 to 2.7 +/- 1.1 mU/L), whereas the decrease in IGF-I was not significant (from 212.9 +/- 26.5 to 162.4 +/- 16.9 micrograms/L).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Placental growth hormone levels in normal pregnancy and in pregnancies with intrauterine growth retardation. 825 74

We studied the efficacy and tolerability of a repeatable long-acting parenteral depot-bromocriptine preparation (Parlodel LAR) in 14 acromegalic patients, 10 of whom had received oral bromocriptine therapy previously, 2 of them showing intolerance to oral bromocriptine. Patients received i.m. injections of 50-100 mg depot-bromocriptine at 4-week intervals for 3-24 months (median 6). Growth hormone profiles were assessed by four daily samples at 4-week intervals. Main daily growth hormone levels decreased from 52.1 +/- 12.3 micrograms/l (mean +/- SEM) to 19.4 +/- 4.7 micrograms/l on the day of injection. In 6 patients, growth hormone values were lowered by more than 50%, whereas IGF-I levels decreased only slightly and growth hormone values during the oral glucose tolerance test remained non-suppressible. Tumour sizes were not affected. Two women became pregnant and were delivered of healthy babies. Side-effects typical of bromocriptine occurred frequently on the days of injection and diminished in most patients after 2 months of therapy despite increasing dosage. Compared with previous oral bromocriptine therapy, 9 of 10 patients preferred the depot preparation, whereas the reduction of growth hormone levels was similar during both treatments. In conclusion, depot-bromocriptine should be considered for acromegalic patients intolerant to oral bromocriptine.
 ...
PMID:Long-term treatment of acromegalic patients with repeatable parenteral depot-bromocriptine. 837 48

Acute and chronic studies in rats have shown that administration of human recombinant insulin-like growth factor I (rhIGF-I) lowers renal vascular resistance and increases RPF, GFR and proximal tubular phosphate absorption. In the present study we examined the effects of subcutaneous injections of rhIGF-I on glomerular and tubular function in eight normal men. Individuals were studied for 5.5 consecutive days in a clinical research center while they ate a constant diet. Four subjects were studied in a non-volume expanded state (Group 1) and four individuals were evaluated during a saline load. From the second to the fourth day, subjects received subcutaneous injections of rhIGF-I, 60 micrograms/kg, at 0800, 1400 and 2000 hours. After commencing the rhIGF-I injections, serum IGF-I levels rose quickly and remained at about three to four times that of baseline throughout the period of rhIGF-I injections. In both the normal and the saline loaded subjects, renal vascular resistance decreased and RPF and GFR (PAH and inulin clearances) rose quickly and were clearly altered within six hours after starting the rhIGF-I injections. RPF had increased by 32 +/- 3% and 33 +/- 2% (grand mean +/- SEM) in the normal and the saline loaded subjects, and GFR rose by 22 +/- 3% and 36 +/- 4% in the two groups. In both groups the absolute and the fractional excretion of phosphate decreased markedly during rhIGF-I treatment, but the absolute and fractional excretion of calcium did not change. The urinary fractional and absolute excretion of albumin and IgG also increased, although slightly, with rhIGF-I injections. There was no consistent effect of IGF-I on tubular sodium handling. These findings demonstrate that in normal men subcutaneous injections of rhIGF-I greatly increase RPF, GFR, and tubular phosphorus reabsorption and enhances microproteinuria.
 ...
PMID:Effects of insulin-like growth factor I on renal function in normal men. 844 Dec 34

Vastus lateralis muscle samples were obtained by needle biopsy from 18 healthy elderly men (65-82 yr) participating in a double blind, placebo (PL)-controlled trial of recombinant human GH (rhGH) and exercise and assessed for muscle morphology and skeletal muscle tissue expression of GH and insulin-like growth factors (IGFs). Subjects initially underwent progressive resistance training for 14 weeks and were then randomized to receive either rhGH (0.02 mg/kg BW.day, sc) or PL while undertaking a further 10 weeks of training. Muscle samples were obtained at baseline and at 14 and 24 weeks. The mean (+/- SEM) cross-sectional areas of type I and II fibers were similar (type I, 3891 +/- 167 microns2; type II, 3985 +/- 200 microns2) at baseline and increased (P < 0.01) by 16.2 +/- 4.1% and 11.8 +/- 3.8%, respectively, after the initial 14-week training period. After treatment (weeks 14-24), two-way repeated measures ANOVA revealed a main effect of time for type I (P < 0.01) and type II fibers (P < 0.05), but no group effect or interaction. The increase in cross-sectional area for the PL group was significant (P = 0.01) for type I (11.5 +/- 3.6%) and approached significance (P = 0.06) for type II fibers (11.1 +/- 5.6%). For rhGH, the change in type I (6.3 +/- 5.9%) and II (7.1 +/- 5.2%) fiber area was not significant. No apparent change in tissue GH receptor, IGF-I, IGF-I receptor, IGF-II, or IGF-II receptor messenger ribonucleic acids occurred as a result of exercise after the 14-week pretreatment period or after treatment with rhGH or PL. These results indicate that rhGH administration in exercising elderly men does not augment muscle fiber hypertrophy or tissue GH-IGF expression and suggests that deficits in the GH-IGF-I axis with aging do not inhibit the skeletal muscle tissue response to training.
 ...
PMID:Lack of effect of recombinant human growth hormone (GH) on muscle morphology and GH-insulin-like growth factor expression in resistance-trained elderly men. 855 Jul 87

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.
 ...
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

Body composition changes with increasing age in men, in that lean body mass decreases whereas fat mass increases. Whether this altered body composition is related to decreasing physical activity or to the known age-associated decrease in growth hormone secretion is uncertain. To address this question, three groups of healthy men (n = 14 in each group), matched for weight, height and body mass index, were investigated using dual-energy X-ray absorptiometry, indirect calorimetry and estimate of daily growth hormone secretion [i.e. plasma insulin-like growth factor I (IGF-I-) levels]. Group 1 comprised young untrained subjects aged 31.0 +/- 2.1 years (mean +/- SEM) taking no regular physical exercise; group 2 consisted of old untrained men aged 68.6 +/- 1.2 years; and group 3 consisted of healthy old men aged 67.4 +/- 1.2 years undergoing regular physical training for more than 10 years with a training distance of at least 30 km per week. Subjects in group 3 had for the past three years taken part in the 'Grand Prix of Berne', a 16.5-km race run at a speed of 4.7 +/- 0.6 min km-1 (most recent race). Fat mass was more than 4 kg higher in old untrained men (P < 0.01, ANOVA) than in the other groups (young untrained men, 12.0 +/- 0.9 kg; old untrained men, 16.1 +/- 1.0 kg; old trained men, 11.0 +/- 0.8 kg), whereas body fat distribution (i.e. the ratio of upper to lower body fat mass) was similar between the three groups. The lean mass of old untrained men was more than 3.5 kg lower (P < 0.02, ANOVA) than in the other two groups (young untrained men, 56.4 +/- 1.0 kg; old untrained men, 52.4 +/- 1.0 kg; old trained men, 56.0 +/- 1.0 kg), mostly because of a loss of skeletal muscle mass in the arms and legs (young untrained men, 24.0 +/- 0.5 kg; old untrained men 20.8 +/- 0.5 kg; old trained men, 23.6 +/- 0.7 kg; P < 0.01, ANOVA). Resting metabolic rate per kilogram lean mass decreased with increasing age independently of physical activity (r = -0.42, P < 0.005). Fuel metabolism was determined by indirect calorimetry at rest. Protein oxidation was similar in the three groups. Old untrained men had higher (P < 0.001) carbohydrate oxidation (young untrained men, 13.2 +/- 1.0 kcal kg-1 lean mass; old untrained men, 15.2 +/- 1.3 kcal Kg-1; old trained men, 7.8 +/- 0.8 kcal kg-1), but lower (P < 0.05, ANOVA) fat oxidation (young untrained men, 10.1 +/- 1.2 kcal kg-1 lean mass; old untrained men, 6.5 +/- 1.0 kcal kg-1; old trained men, 13.7 +/- 1.0 kcal kg-1) than the other two groups. Mean plasma IGF-I level in old trained men was higher than in old untrained men (P < 0.05), but was still lower than that observed in young untrained men (P < 0.005) (young untrained men, 236 +/- 24 ng mL-1; old untrained men, 119 +/- 13 ng mL-1; old trained men, 166 +/- 14 ng mL-1). In summary, regular physical training in older men seems to prevent the changes in body composition and fuel metabolism normally associated with ageing. Whether regular physical training in formerly untrained old subjects would result in similar changes awaits further study.
 ...
PMID:Effect of regular physical training on age-associated alteration of body composition in men. 873 84

Reduced insulin-like growth factor bioactivity has been linked to poor metabolic control and growth hormone hypersecretion in adolescents with Type 1 diabetes. The safety and efficacy of recombinant human insulin-like growth factor I administered subcutaneously in a dose of 40 micrograms kg-1 for 28 days was studied in a group of 6 adolescent male subjects with Type 1 diabetes (aged 13.6-19.4 years, puberty stage 3-5). After a 4-week run-in period (week -4 day 0) recombinant human insulin-like growth factor I was administered for 4 weeks (day 0 to week +4) before a run-out of a further 4 weeks duration (week +4 to +8). HbA1c levels were measured throughout the study and overnight profiles were undertaken to study levels of insulin-like growth factor 1, insulin-like growth factor binding protein-3, and growth hormone concentrations (week -1, day 0, and week +4). The injections were well tolerated and hypoglycaemia was not problematic at any stage of the study. Recombinant insulin-like growth factor I administration appeared to lead to a sustained increase in insulin-like growth factor I levels (week -1; 198 +/- 16 ng ml-1, week +4; 422 +/- 18 ng ml-1, mean +/- SEM; p = 0.03). Insulin-like growth factor binding protein-3 concentrations (n = 6) increased in 5 subjects (week -1; 4.5 +/- 0.3 micrograms ml-1, week +4; 5.1 +/- 0.4 micrograms ml-1) and mean overnight growth hormone decreased (week -1; 14.0 +/- 3.1 mUI-1, week +4; 7.6 +/- 1.7 mUI-1) during the period of study but these differences were not statistically significant. HbA1c levels fell significantly at the time of rhIGF-I administration (day 0; 10.4 +/- 1.9% vs week +4; 9.4 +/- 1.9%; p = 0.03) despite a reduction in subcutaneous isophane insulin dose from 0.50 +/- 0.02 U kg-1 to 0.41 +/- 0.02 U kg-1 (p = 0.03). There was no significant change in biochemical and haematological indices, glomerular filtration rate or urinary albumin excretion. The restoration of IGF-I levels in adolescents with Type 1 diabetes may have a beneficial impact on glycaemic control.
 ...
PMID:The effects of repeated daily recombinant human insulin-like growth factor I administration in adolescents with type 1 diabetes. 884 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>