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)

IM-9 cultured human lymphocytes were treated with N-linked glycosylation inhibitors, N-linked oligosaccharide processing inhibitors, or neuraminidase to study the effect of glycosylation modification on human growth hormone binding and molecular weight of surface hGH receptor. One mg/l tunicamycin and 20 mmol/l glucosamine decreased 125I-hGH binding to the cells to 46.3 +/- 2.4% (mean +/- SEM) and 21.9 +/- 0.2% of the controls, respectively. The hGH binding was 33.0 +/- 18.4% of the control value in the cells treated with monensin. The inhibition of binding was due to a decrease in the hGH receptor number without any affinity changes in these cells. Neither 1 mg/l swainsonine nor 100 mg/l castanospermine had any effect on the hGH binding. On the other hand, 125I-hGH binding to neuraminidase-treated cells was significantly enhanced with accompanying affinity changes. When 125I-hGH was cross-linked to IM-9 cells, there were no differences in the molecular weight of hGH receptor complexes (140 K) between untreated cells and cells treated with tunicamycin, glucosamine, monensin, or castanospermine. However, the 128 K hGH-receptor complex appeared in swainsonine-treated cells; this complex was sensitive to endoglycosidase H. These data show that the altered carbohydrate moiety changed hGH binding and the size of surface hGH receptor and suggest that glycosylation of receptor is important for the binding of hGH and for its physiological action.
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PMID:Effects of glycosylation inhibitors on human growth hormone receptor in cultured human lymphocytes. 314 7

Daily injections of methionine-free, recombinant hGH (rhGH), 8 IU, were administered in six healthy volunteers. Non-esterified fatty acid levels increased significantly from 0.45 +/- 0.06 to 1.08 +/- 0.05 mEq/litre (mean +/- SEM) at 4 hours after the first injection of rhGH (p less than 0.001). Plasma IGF-1 levels increased significantly at 24 hours after each of the four daily injections of rhGH (basal, 0.80 +/- 0.06 units/ml; 24 hours, 1.72 +/- 0.21 units/ml; 48 hours, 3.22 +/- 0.42 units/ml; 72 hours, 3.17 +/- 0.49 units/ml; 96 hours, 3.63 +/- 0.32 units/ml; p less than 0.001). Eleven patients with hGH deficiency were treated with rhGH, 0.5 IU/kg/week for 3 months. Their heights increased by between 1.1 cm and 4.1 cm during the 3 months of treatment, which was calculated to be equivalent to 4.4-16.4 cm/year, with a mean height velocity of 8.6 +/- 1.1 cm/year. Anti-hGH antibody was observed in one patient treated with rhGH and had a titre of 10.
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PMID:Current clinical trials with authentic recombinant human growth hormone in Japan. 329 43

Recombinant somatropin, produced by recombinant DNA technology, was administered by injection in daily doses of 8 IU to six healthy young volunteers. Daily injection for 4 days did not cause any significant change in the results of physical examination, blood count or urinalysis. Non-esterified fatty acid levels increased significantly from 0.45 +/- 0.16 to 1.08 +/- 0.12 mEq/litre (mean +/- SEM) at 4 hours after the first injection (p less than 0.001). Plasma IGF-1 levels increased from 0.80 +/- 0.14 units/ml to 1.72 +/- 0.50, 3.22 +/- 1.02, 3.17 +/- 1.20 and 3.63 +/- 0.78 units/ml at 24 hours after each daily injection for 4 days (p less than 0.001). Plasma hGH reached peak levels at 3 hours after intramuscular injection of recombinant somatropin, 4 IU, and this peak value was 57.3 +/- 2.8 ng/ml. A total of 21 patients with pituitary dwarfism were also treated with recombinant somatropin for 6 months at a dose of 0.5 IU/kg/week. Their heights increased by 2.2-5.0 cm during the 6 months of treatment, which was calculated to be equivalent to 4.4-10.0 cm/year with a mean growth rate of 7.4 +/- 0.4 cm/year. Anti-hGH antibody with a titre of 10 was observed in two patients at the end of 6 months of treatment.
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PMID:Clinical trial with authentic recombinant somatropin in Japan. 330 Jan 51

A total of 21 patients with Turner's syndrome were treated with pituitary hGH and/or somatrem for 1-2 years. Plasma non-esterified fatty acid increased significantly from 0.52 +/- 0.06 to 1.30 +/- 0.09 mEq/litre at 4 hours after injection of hGH, 4 IU (mean +/- SEM, p less than 0.001). Basal plasma IGF-1 levels were within the normal range; however, they increased significantly at 24 hours after the first three daily injections of hGH, 4 IU (basal, 0.92 +/- 0.14 units/ml; 24 hours, 1.39 +/- 0.16 units/ml; 48 hours, 1.68 +/- 0.19 units/ml; 72 hours, 1.91 +/- 0.22 units/ml; p less than 0.001). For long-term treatment, patients were given hGH, 4-16 IU for 1-2 years. Their height velocity increased to 5.5 +/- 1.2 cm/year and 5.1 +/- 0.6 cm/year in the first and second year of the treatment, respectively. These values were greater than the pretreatment value of 3.6 +/- 0.8 cm/year (p less than 0.001). Antibody against hGH was observed in 60% of the patients at the end of 12 months of somatrem treatment. Otherwise there were no significant changes in physical, blood or urine examinations. These results indicate that hGH treatment is useful for the acceleration of growth velocity in patients with Turner's syndrome.
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PMID:Growth hormone treatment in Turner's syndrome. 347 92

Twenty patients with Turner's syndrome were treated with methionyl human growth hormone (met-hGH) produced by recombinant DNA technology. Plasma non-esterified fatty acid (NEFA) (mean +/- SEM) increased significantly from 0.52 +/- 0.06 to 1.30 +/- 0.09 mEq/l at 4 h after the first administration of 4 IU of met-hGH (P less than 0.001). Basal plasma somatomedin C (SM) levels were within the normal range; however, they increased significantly at 24 h after the first three daily injections of 4 IU of met-hGH (basal, 0.92 +/- 0.14; 24 h, 1.39 +/- 0.16; 48 h, 1.68 +/- 0.19; 72 h, 1.91 +/- 0.22 U/ml; P less than 0.001). For long-term treatment, the patients were given 16 IU of met-hGH per week for 6 months. The height increase during treatment was greater in 16 patients, but smaller in 4 than before treatment. The heights increased between 1.4 and 3.7 cm during 6 months of treatment, which corresponds to between 2.8 and 7.4 cm/year. The mean increase of 5.7 +/- 0.4 cm/year was greater than the pretreatment value of 3.7 +/- 0.2 cm/year (P less than 0.001). There was a positive correlation between growth rate and maximum increase in SM (r = 0.51, P less than 0.05). Antibody against hGH appeared in 3 patients after 2 months; 10 of the 20 patients had antibody after 6 months of treatment. However, the antibody did not suppress the growth effect of met-hGH. Otherwise there were no significant changes in physical, blood, or urine examinations. These results indicate that hGH treatment is useful for the acceleration of growth velocity in patients with Turner's syndrome.
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PMID:Treatment of Turner's syndrome with methionyl human growth hormone for six months. 352 Nov 83

Glucose metabolism during fasting was investigated in 10 children aged 1.5 month-11.5 yr with deficiency of GH with or without other pituitary hormone deficiencies. After 10-16 h of fasting, mean plasma glucose was 56 +/- 4 (SEM) mg/dl, the result of decreased hepatic production of glucose (3.3 +/- 0.3 mg kg-1 min-1) insufficient to match glucose utilization (3.6 +/- 0.4 mg kg-1 min-1). The diminution of plasma glucose and of glucose production was similar whether ACTH deficiency was present (3.2 +/- mg kg-1 min-1) or not (3.5 +/- 0.6 mg kg-1 min-1). These results indicate that the lack of GH was the primary cause of hypoglycemia. Fasting plasma alanine (212 +/- 41 mumol/liter) and lactate (1222 +/- 136 mumol/liter), the main gluconeogenic substrates, were normal and did not correlate with the decrease of hepatic glucose release. Both plasma FFA (552 +/- 35 microM) and beta-hydroxybutyrate (654 +/- 158 microM) were in the low normal range, and neither correlated with the rate of glucose utilization. hGH replacement therapy resulted in a normalization of fasting plasma glucose concentration (78.5 +/- 6 mg/dl, P less than 0.005) and hepatic glucose production (6.1 +/- 1.2 mg kg-1 min-1). No significant changes occurred in the plasma concentrations of gluconeogenic or lipid substrates. These results, together with the known stimulatory effects of GH on carbohydrate-induced insulin secretion and storage of hepatic glycogen, suggest that the changes in glucose production in untreated and GH treated patients reflect the degree of hepatic glycogen replenishment.
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PMID:Effects of hypopituitarism and growth hormone replacement therapy on the production and utilization of glucose in childhood. 390 70

Previous studies have shown that adipocytes isolated from normal rats possess specific receptors for growth hormone (GH). Thus, we have now investigated the direct effects on such cells of GH added in vitro. The biological actions of GH determined were the stimulation of 14C-glucose oxidation to 14CO2 and conversion to 14C-lipid. As in adipose segments, hGH stimulation of these parameters required a 3-4 hr preincubation period in GH-free medium. The effect of hGH or bGH was dose-dependent with maximal effects at 1-2 micrograms/ml (CO2 55 +/- 13% stimulation above basal n = 9; lipid 33 +/- 4% n = 21, mean +/- SEM). The magnitude of the effect in isolated adipocytes was lower than that seen in adipose segments from similar groups of animals (lipid 67 +/- 26%, n = 4). The induction of responsiveness by preincubation was accompanied by a parallel increase in 125I-hGH binding. These studies have demonstrated that adipocytes from normal rats not only possess specific receptors for GH but also are metabolically responsive to GH added in vitro. These data suggest that the isolated rat adipocyte should be a useful model for further investigation of the relationship between GH receptor and post-receptor events.
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PMID:Demonstration of in vitro actions of growth hormone on isolated rat adipocytes. 396 42

Corticotropin-releasing factor [(CRF) 200 micrograms] was administered iv to five patients with classical pituitary-dependent Cushing's disease and to five normal subjects. In both groups no changes were observed in the plasma concentrations of hGH, PRL, TSH, LH, or FSH. In the normal subjects plasma ACTH levels rose from 41 +/- 9 (SEM) pg/ml to 87 +/- 28 pg/ml after 60 min (P less than 0.01) and plasma cortisol levels from 0.30 +/- 0.06 mumol/liter (8.0 +/- 0.2 micrograms/dl) to 0.53 +/- 0.07 mumol/liter (14.2 +/- 0.2 micrograms/dl) after 60 min (P less than 0.001). In the patients with classical Cushing's disease plasma ACTH levels increased from 109 +/- 23 to 281 +/- 78 pg/ml after 30 min (P less than 0.01) and plasma cortisol levels from 0.45 +/- 0.06 mumol/liter (12.0 +/- 0.2 micrograms/dl) to 1.02 +/- 0.21 mumol/liter (27.2 +/- 0.6 micrograms/dl) after 120 min (P less than 0.005). The absolute increments of ACTH and cortisol levels in the patients with Cushing's disease were significantly (P less than 0.02 and P less than 0.05, respectively) higher than in the normal subjects. In individual patients, however, CRF responses were rather variable; three of the patients had ACTH or cortisol increases within the mean +/- SD of the responses of the control subjects. In another patient with Cushing's disease due to bilateral macro- and micronodular adrenocortical hyperplasia, who had nonsuppressible circulating ACTH and cortisol levels, unresponsiveness to CRF was shown. These results indicate that testing the pituitary-adrenocortical axis of patients with Cushing's disease may reveal hyperresponsiveness, normal responsiveness, and even unresponsiveness.
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PMID:Responsiveness of the hypophyseal-adrenocortical axis to corticotropin-releasing factor in pituitary-dependent Cushing's disease. 630 29

A significant impediment to studies of growth disorders in man has been the lack of an easily accessible target tissue for studies of GH action. As human fibroblasts have been shown to produce a somatomedin-C-like peptide in culture, the aim of this study was to investigate the interaction of GH with cultured fibroblasts. GH binding to human skin fibroblasts and to lung fibroblasts was examined. Specific binding of [125I]iodo human GH [( 125I]iodo hGH) was rapid, reversible, and time and temperature dependent. Maximal binding was achieved within 2 h at 30 C and specifically bound [125I]iodo-hGH was rapidly dissociable at this temperature. A linear relationship between specific binding of [125I]iodo-hGH and cell number was found and negligible degradation of labeled hormone occurred during the binding studies. Half-maximal inhibition of specific binding occurred at 30 ng/ml hGH. Lactogenic and nonprimate somatogenic hormones did not displace [125I]iodo-hGH at the concentrations tested. Scatchard analysis of [125I]iodo-hGH binding to human skin fibroblasts demonstrated a single class of binding sites with an affinity constant of 1.07 +/- 0.07 (SEM, n = 5) X 10(9) M-1 and a capacity of 8355 +/- 1880 site per cell. Similar GH-receptor characteristics were found on each of the fibroblast cell lines examined irrespective of the site of origin (skin or lung) or age of donor. These findings demonstrate for the first time specific GH receptors in cultured human fibroblast cell lines. The demonstration of GH receptors in human fibroblasts should encourage the search for similar receptors in tissues not previously considered to be target tissues for GH action. On the basis of these studies we suggest that cultured skin fibroblasts may be a suitable tissue for the study of GH-receptor status in patients with disorders of growth.
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PMID:Identification and characterization of specific growth hormone receptors in cultured human fibroblasts. 631 29

The in vitro stimulation of [3H]thymidine uptake into lectin-activated lymphocytes in the presence of various sera was studied. The mean precision of the assay is 5%, and the study of the confidence intervals shows variations from 4% to 12%. Compared to a normal reference serum (fixed as 1 U/ml), the serum thymidine uptake stimulating activity (mean +/- SEM) was 1.04 +/- 0.07 U/ml in normal adult males, 2.63 +/- 0.48 U/ml in acromegalic patients, 1.51 +/- 0.13 U/ml in constitutional dwarfism and 0.37 +/- 0.04 U/ml in untreated hypopituitary dwarfism with a significant difference between the groups (P less than 0.001). In patients with hypopituitarism a single im hGH dose (6 mg/m2 increased the thymidine uptake stimulating activity of serum within 24 to 48 h following injection. The effects of directly adding hGH, insulin and T3 to the assay, have been studied: pharmacological concentrations are required to produce only a slight effect. Physiological concentration of a purified preparation of somatomedin A stimulated thymidine uptake and its effect is increased in the presence of serum. These data demonstrate that [3H]thymidine uptake into lectin-activated lymphocytes is stimulated by a GH-dependent serum factor. The data suggest that this method should be proposed for an accurate and sensitive biological evaluation of serum thymidine uptake stimulating activity.
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PMID:A hormonally controlled serum factor stimulating the thymidine uptake into lectin-activated lymphocytes. 702 10


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