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)

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

A high-affinity growth hormone-binding protein (GHBP) in serum is derived from the extracellular domain of the GH receptor. In an attempt to investigate the differences in GHBP levels in various conditions of poor growth, we measured GHBP levels by two methods--an Ultrogel chromatographic technique and a ligand-mediated immunofunctional assay (LIFA). The following three groups of children were studied: Turner's syndrome (n = 7), idiopathic and/or familial short stature ([ISS] n = 15), and organic or idiopathic hypopituitarism (n = 19). All groups were similar in age (Turner's syndrome, 10.1 +/- 0.9 years; ISS, 10.0 +/- 0.7; hypopituitarism, 11.5 +/- 1.0) and height SEM score (Turner's syndrome, -2.9 +/- 0.3; ISS, -3.0 +/- 0.4; hypopituitarism, -2.3 +/- 0.4). Their values were compared with those values of GHBP in healthy controls of similar age. Immunofunctional assay values for GHBP were as follows: Turner's syndrome, 235.4 +/- 26.0 pmol/L; ISS, 122.4 +/- 11.0; and hypopituitarism, 157.1 +/- 23.0. These results were significantly different in subjects with ISS and hypopituitarism as compared with a group of healthy controls between the ages of 9 and 12 years (N = 255; GHBP = 287.9 +/- 10.9 pMol/L; P < .001 compared with both ISS and hypopituitarism). Similar changes were found using Ultrogel chromatography. This difference in GHBP levels is still significant even when more stringent criteria are applied to define hypopituitarism (ie, peak GH responses to stimuli < 6.0 ng/mL, instead of < or = 10 ng/mL originally).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Growth hormone-binding protein levels: studies of children with short stature. 813 84

While circulating GH concentrations are high in fetal life, skeletal growth is only slightly reduced by GH deficiency in utero. This has been explained by the relatively low binding of GH to fetal hepatic tissue, suggesting a lack of GH receptors (GHR). The GHR also recognizes ovine placental lactogen (oPL), which may have a specific role either as a fetal growth-promoting hormone or in regulating fetal metabolism. We investigated GHR expression and membrane binding of ovine (o) GH and oPL in various ovine fetal tissues and in maternal liver at different gestational stages. Singleton-bearing ewes at 51, 95, and 120 days gestation were killed. Liver, muscle, kidney, and brain samples were taken from the fetuses as well as placentas and livers from the ewes (n = 3/gestational age). GHR mRNA measured by Northern blot analysis was expressed at high levels in maternal liver at all gestational stages. A major band was observed at 4.4 kilobases (kb), and three minor bands were observed at 2.5, 1.7, and 8.1 kb. In fetal and placental tissue, only the 4.4-kb band was detected. This was present as early as day 51 of gestation in liver, kidney, lung, heart, and placenta and increased slightly with advancing gestation. On day 51, the expression of GHR mRNA in muscle was negligible, but by day 95, muscle expressed higher concentrations than fetal liver. Placental samples showed only a slight signal, with no change over the gestational range studied. In situ hybridization revealed the placental mRNA to be primarily associated with the decidua. Hepatic tissue showed specific binding to [125I]oGH and [125I]oPL from 51 days gestation. [125I]oPL showed a higher [51 days, 17.9 +/- 1.9% (mean +/- SEM); 95 days, 11.5 +/- 1.6%; 120 days, 16.3 +/- 0.9%] specific binding to the liver membranes than [125I]oGH (51 days, 2.1 +/- 0.7%; 95 days, 2.6 +/- 0.3%; 120 days, 3.5 +/- 0.4%). We conclude that oGHR are present as early as day 51 of gestation in various tissues, including liver. The message appears later in skeletal muscle than in liver. As the GH receptor binds oPL with higher potency than oGH, the parallel ontogenic changes in [125]oGH and [125]oPL binding in the liver do not support the presence of a PL receptor under independent developmental regulation.
 ...
PMID:Tissue distribution and ontogeny of growth hormone receptor messenger ribonucleic acid and ligand binding to hepatic tissue in the midgestation sheep fetus. 844 Jan 72

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

GH-binding protein (GHBP) is increased in obesity. It is not known whether the increase in GHBP is reversible with weight loss or modulated by acute changes in nutritional intake. To address these questions, we measured GHBP in 18 obese subjects [body mass index (BMI), 40.9 +/- 1.1 kg/m2 (mean +/-SEM)] before and after an average weight loss of 30.3 +/- 4.6 kg and in 18 age- and sex matched normal subjects (BMI, 23.0 +/- 0.4 kg/m2) and studied the effects of a very low calorie diet over 4 days in 5 normal subjects and a subgroup of obese subjects before (n = 6) and after (n = 5) weight loss. GHBP was elevated in the obese subjects compared to levels in age- and sex-matched normal controls (1.48 +/- 0.1 vs. 0.53 +/- 0.1 nmol/L; P < 0.0001). GHBP was positively correlated to BMI and waist circumference (r = 0.71; P < 0.00001 and r = 0.73; P < 0.00001, respectively). In addition, GHBP was positively correlated to insulin as well as proinsulin levels (r = 0.60; P < 0.001 and r = 0.55; P < 0.001, respectively). After diet-induced massive weight loss, GHBP levels were restored to normal in obese subjects (BMI, 27.8 +/- 1.4 kg/m2). Multiple stepwise regression analysis revealed that changes in waist circumference and abdominal sagittal diameter during weight loss were the major determinants of and accounted for 54% of the fall in GHBP levels. Neither insulin nor proinsulin was an independent predictor. No changes were observed in GHBP in normal, obese, or reduced weight obese subjects after 4 days of a very low calorie diet, although mean insulin levels fell significantly in the normal subgroup as well as in the obese subgroup studied after weight loss. In summary, GHBP levels are elevated in obesity, are restored to normal by massive weight loss, and are unaffected by short term hypocaloric feeding. We conclude that GHBP may be regulated by the same or closely related factors that regulate fat mass and abdominal fat mass in particular, but not by insulin or acute changes in nutrition.
 ...
PMID:Serum growth hormone-binding protein in obesity: effect of a short-term, very low calorie diet and diet-induced weight loss. 863 61

Sf21 insect cells were infected with recombinant baculovirus containing cDNA for the entire coding region of the mouse growth hormone binding protein (mGHBP). Recombinant (r) mGHBP was expressed at a yield of 17.3 mg/liter/3 days. The molecular size (Mr) of the rmGHBP was approximately 33,000 as estimated by SDS-PAGE. Amino-terminal sequence analysis of the recombinant protein yielded two sequences: one identical to amino acids l- 15 and another corresponding to amino acids 14-21 of the GHR/GHBP. Western blot analysis revealed that this is the same Mr as that of one of the two major Mr forms of serum mGHBP. Deglycosylation of serum mGHBP and recombinant mGHBP caused a shift in the molecular size of both proteins to that expected after removal of all N-linked carbohydrates. Binding characteristics of the recombinant mGHBP to mouse growth hormone were similar to those for serum GHBP. Scatchard analysis showed an equilibrium association constant (Ka) for rmGHBP of 3.8 x 10(8) +/- 0.6 x 10(8) M(-1) (mean +/- SEM, n = 3) and Ka of 9.2 x 10(8) +/- 2.0 x 10(8) M(-1) (mean +/- SEM, n = 3) for the serum mGHBP. In conclusion, this expression system should allow a production of relatively large quantities of mGHBP suitable for physiological studies on the role of this protein.
 ...
PMID:Purification and characterization of recombinant mouse growth hormone binding protein produced in the baculovirus expression system. 917 86

Previous workers have suggested that guinea pig serum does not contain a GH-binding protein (GHBP) or that it is defective. The current studies, however, have identified and characterized the presence of GH-binding activity in guinea pig serum using gel chromatography to separate bound and free hormone. The detection of GH-binding activity is critically reliant on the type of radioligand used to measure binding. Clear identification of GH-binding activity was demonstrated with [125I]ovine GH (oGH), but specific binding could not be measured with [125I]human GH. The novel specificity was also shared by guinea pig liver membrane GH receptor (GHR) and cytosol GHBP, suggesting structural similarity in the GH-binding domain between the GHR and soluble GHBPs. The binding of oGH was dependent on serum concentration (5 microl serum produced 16.03 +/- 0.5% specific binding; mean +/- SEM; n = 11) and incubation time (equilibrium was reached by approximately 6 h at 21 C) and was completely reversible (t(1/2), approximately 2 h). Scatchard analysis revealed linear plots with an affinity constant (Ka) of 0.59 +/- 0.09 x 10(9) M(-1) and a capacity of 23,181 +/- 4,474 fmol/ml serum. Similar association constants were obtained for liver membrane GHR (0.79 +/- 0.22 x 10(9) M(-1)) and cytosol GHBPs (0.99 +/- 0.15 x 10(9) M(-1)), but the capacity, when expressed as femtomoles per g tissue, was significantly increased (4-fold) in cytosol (4,303 +/- 505) over that in membranes (1,071 +/- 257). There was no sex difference in Ka or level of GHBP in guinea pig serum. Surprisingly, the level of GH-binding activity was very low to undetectable in pregnant guinea pig serum. Characterization of the native structure of guinea pig GHBPs has indicated the presence of several proteins that are structurally distinct. Although the distribution of GH-binding activity covered a large Mr range (approximately 70-350 kDa) the major form of the circulating GHBP identified by gel chromatography had an apparent native Mr of 150-170 kDa. Partially purified GHBP (approximate Mr, 170 kDa) was covalently cross-linked to [125I]oGH and subjected to nonreducing SDS-PAGE. Specific GHBP complexes of 158 and 85 kDa were detected, suggesting that the partially purified GHBP complex may be composed of a smaller GHBP associated noncovalently with a non-GH-binding protein. "Pore limit" native PAGE (cathodic and anodic) revealed the presence of specific GHBPs of 363, 158, 74, and 55 kDa, which cross-hybridized with the rat liver membrane GHR monoclonal antibody mAb 263 but not with the rat serum GHBP-specific mAb 4.3. Interestingly, although GH binding was undetectable in pregnant guinea pig serum, Western immunoblot analysis with mAb 263 demonstrated the presence of a major immunoreactive GHBP band of 105 kDa in addition to 158- and 55-kDa GHBPs. The data indicate that the GHBPs are immunologically related to the rat membrane GHR, but provide no evidence to support the presence of a hydrophilic tail sequence homologous to that in the rat GHBP. These studies have identified in guinea pig serum GHBPs that exhibit novel ligand specificity, structural heterogeneity, and an immunological relationship to the rat liver membrane GHR. The identification of serum GHBP and the novel ligand specificity, which is also expressed by the liver membrane GHR, argue against the view that the guinea pig has a defective GHBP.
 ...
PMID:Guinea pig serum contains a specific high affinity growth hormone-binding protein with novel ligand specificity. 927 37

We have examined whether alterations in the growth hormone/insulin-like growth factor-1 axis play a role in the pathogenesis of psoriasis. Serum, urine, full skin biopsies, and suction blister roofs were obtained from patients with psoriasis and from healthy controls. Serum concentrations of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 were measured by radioimmunoassay. Growth hormone-binding protein was measured by ligand-mediated immunofunctional assay. Growth hormone concentration in urine was measured by an immunometric assay, and growth hormone receptor-gene expression was measured by RNase protection assay or by quantitative reverse transcriptase polymerase chain reaction in total RNA isolated from epidermal suction blister roofs. Serum concentrations of insulin-like growth factor-1 (249 +/- 12 micrograms per liter, mean +/- SEM, n = 42, and 277 +/- 21 micrograms per liter, n = 9, for psoriatic patients and controls, respectively), insulin-like growth factor binding protein-3 (3.1 +/- 0.08 mg per liter, n = 42, and 3.3 +/- 0.22 mg per liter, n = 9), growth hormone-binding protein (344 +/- 65 pmol per liter, n = 10, and 311 +/- 83 pmol per liter, n = 9), urinary growth hormone excretion during 24 h (12.8 +/- 2.7 microIU per 24 h, n = 12, and 12.3 +/- 1.6 microIU per 24 h, n = 9), and epidermal growth hormone receptor gene expression [32 +/- 12 x 10(3) mRNA transcripts per microgram total RNA (involved skin), n = 11, and 47 +/- 14 x 10(3) mRNA transcripts per microgram total RNA, n = 9] were similar in patients and controls. For insulin-like growth factor-1 and insulin-like growth factor binding protein-3 the values in psoriatic patients were also similar to those in larger control groups, n = 195 and n = 400, respectively. In addition, we found no evidence of local expression of growth hormone or prolactin in full skin punch biopsies from psoriatic involved skin by reverse transcriptase polymerase chain reaction. In conclusion, our results suggest that alterations in the growth hormone/ insulin-like growth factor-1 axis do not play a major role in the pathogenesis of psoriasis.
 ...
PMID:No evidence for involvement of the growth hormone/insulin-like growth factor-1 axis in psoriasis. 934 96

In vivo administration of GH induces lipolysis and lipid oxidation. However, it is not clear whether the stimulation of lipid oxidation is a direct effect of GH or is driven by increased substrate supply secondary to lipolysis. An in vitro bioassay has been established for assessing beta-oxidation of fatty acids in mitochondria, based on the measurement of conversion of tritiated palmitic acid to 5H2O by fibroblasts in culture. We have modified this assay to investigate whether GH stimulates fatty acid oxidation. GH stimulated oxidation of palmitic acid maximally by 26.7 +/- 2.5% (mean +/- SEM; P < 0.0001). The stimulation was biphasic, with the oxidation rate increasing with increasing GH concentration to a peak response at 1.5 nmol/L and declining to a level not significantly different from control thereafter. Insulin-like growth factor-I at concentrations of up to 250 nmol/L had no significant effect on fatty acid oxidation. GH-binding protein attenuated the effect of GH. An anti-GH receptor (GHR) antibody (MAb263), which dimerizes the receptor and induces GH-like biological actions, significantly stimulated fatty acid oxidation. Another anti-GHR antibody (MAb5), which prevents receptor dimerization, suppressed GH action. In summary, GH directly stimulated fatty acid oxidation, an action not mediated by insulin-like growth factor-I. Dimerization of GHRs was necessary for this effect. This bioassay is a practical tool for studying the regulatory effects of GH on lipid oxidation.
 ...
PMID:Stimulation of mitochondrial fatty acid oxidation by growth hormone in human fibroblasts. 939 41

Acquired GH resistance together with reduced skeletal muscle mass are found in patients with increased protein catabolism due, for example, to sepsis, trauma, or major surgery. Both administration of glutamine-containing parenteral nutrition and GH treatment have been found to diminish this catabolism. The effects of GH are mediated in part by insulin-like growth factor I (IGF-I) that is produced in the liver and locally in GH target tissues. The aim of this study was to investigate the effect of GH treatment on expression of the IGF-I gene and GH receptor (GHR) gene in skeletal muscle after major surgery. A new quantitative RT-PCR-based assay was established to measure IGF-I gene expression. Metabolically healthy patients, without significant preoperative weight loss, who were undergoing elective abdominal surgery were included in the study. Five patients (one woman and four men) were treated with daily injections of GH (0.3 IU/kg.day) in addition to being given total parenteral nutrition including glutamine (0.28 g/kg.day). The control group consisted of eight patients (three women and five men), who were given glutamine-enriched total parenteral nutrition but no GH. A muscle biopsy was taken from the lateral portion of the quadriceps femoris muscle preoperatively (day 0) after induction of anesthesia. A second biopsy was taken under local anesthesia on postoperative day 3. Total ribonucleic acid (RNA) was extracted from the muscle biopsies, and IGF-I messenger RNA (mRNA) and GHR mRNA were measured by competitive quantitative RT-PCR assays. IGF-I mRNA and GHR mRNA levels were related to the expression of a housekeeping gene (cyclophilin). In the control group, IGF-I mRNA levels decreased from 1505 +/- 265 (mean +/- SEM) transcripts/cpm cyclophilin on day 0 to 828 +/- 172 on day 3 (P < 0.05). In contrast, IGF-I mRNA levels did not change in the GH-treated group (1188 +/- 400 transcripts/cpm cyclophilin on day 0 vs. 1089 +/- 342 transcripts/cpm cyclophilin on day 3). No statistically significant changes were seen in GHR expression. We conclude that administration of GH prevents the reduction in IGF-I gene expression in skeletal muscle after abdominal surgery.
 ...
PMID:Growth hormone treatment prevents the decrease in insulin-like growth factor I gene expression in patients undergoing abdominal surgery. 958 57


<< Previous 1 2 3 4 Next >>