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Christian J Strasburger

Publications and source records attributed to Christian J Strasburger.

At least 19 recordsLinked to original sources
PubMed2006

Anxiety modulation by the heart? Aerobic exercise and atrial natriuretic peptide.

Exercise has an anxiolytic activity and it increases the concentrations of atrial natriuretic peptide (ANP). Because ANP has an anxiolytic activity, this hormone might contribute to the anxiolytic effects of aerobic exercise. Cholecystokinin-tetrapeptide (CCK-4)-induced panic attacks were studied in 10 healthy subjects after "quiet rest" or 30 min of aerobic exercise. Plasma ANP concentrations were measured before and after exercise or quiet rest using a commercial IRMA kit. Compared to quiet rest, CCK-4-induced anxiety was reduced and plasma ANP concentrations were increased by prior exercise. This anxiolytic activity of exercise was correlated with the increase in plasma ANP concentrations. Our results suggest that besides other mechanisms, ANP might be a physiologically relevant humoral link between the heart and anxiety-related behavior contributing to the acute anxiolytic effects of exercise.

Adult↗
PubMed2006

Comparative pharmacokinetics and pharmacodynamics of a new sustained-release growth hormone (GH), LB03002, versus daily GH in adults with GH deficiency.

CONTEXT: LB03002 is a novel sustained-release GH preparation administered once weekly. OBJECTIVE: Our objective was to examine the pharmacokinetics, pharmacodynamics, and safety of LB03002 vs. daily GH. DESIGN AND SETTING: This open-label, crossover study compared the pharmacokinetics and pharmacodynamics of LB03002 and daily GH. PATIENTS AND OTHER PARTICIPANTS: Six male and three female patients with adult GH deficiency participated in the single-center study. INTERVENTION: Subjects were on stable daily GH treatment before the study. After a 4-wk washout with no GH, five weekly doses of LB03002 were given. MAIN OUTCOME MEASURE: GH and IGF-I concentrations were measured during the last dose of daily GH and during the first and fifth weekly doses of LB03002. RESULTS: The observed maximal serum GH concentration was approximately doubled after LB03002 (6.1 +/- 3.2 and 4.5 +/- 2.2 microg/liter at first and fifth doses) compared with daily GH (2.7 +/- 2.2 microg/liter). A sustained increase in GH concentration for more than 48 h was observed with LB03002, such that dose-normalized area under the curve (AUC) was not significantly different between daily GH and LB03002. Mean maximal serum IGF-I concentration was 34-41% greater with LB03002 than with daily GH, and AUC was 7-fold greater. However, normalized to GH dose, AUC for IGF-I was comparable. Adverse events and local reactions were acceptable, and there were no evident safety concerns with LB03002. CONCLUSIONS: Multiple weekly doses of LB03002 appeared safe and well tolerated. Comparable GH bioavailability and sustained IGF-I elevations support the use of once-weekly LB03002 to replace daily GH therapy.

Adult↗
PubMed2006

Identification of a monoclonal antibody against the leptin receptor that acts as an antagonist and blocks human monocyte and T cell activation.

Nutritional status has a major impact on the immune response and this is in part mediated by leptin, a pro-inflammatory cytokine. Preliminary data suggest that antagonism of leptin may offer a therapeutic approach for the treatment of some inflammatory disorders. We have tested monoclonal antibodies (mAbs) to the human leptin receptor (ObR) for antagonist activity using a leptin signalling bioassay. We identified a mAb, 9F8, which demonstrated dose-dependent antagonist activity in the leptin bioassay. Specificity of the mAb for ObR was confirmed using a plate binding assay. The 9F8 mAb displaced leptin binding to human ObR and enzymatically generated Fab fragments of 9F8 retained antagonist activity. Therefore the Fab fragment of 9F8 was cloned and recombinant 9F8 Fab (rFab) was purified from E. coli periplasmic fraction using a C-terminal His tag. Purified 9F8 rFab bound to human ObR and exhibited leptin antagonist activity. In vitro studies demonstrated that the 9F8 mAb inhibited leptin induced TNF-alpha production from human monocytes and anti-CD3 mAb induced proliferation of human T cells in PBMC culture. In conclusion, this study has identified a mAb to the human leptin receptor which inhibits leptin signalling and acts as a leptin antagonist in vitro.

Antibodies, Monoclonal↗
PubMed2006

Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on IGF-I levels, tumor mass, hypertension and glucose tolerance.

OBJECTIVE: We aimed to investigate the efficacy of pegvisomant in patients with acromegaly resistant to long-term (> or = 24-month), high-dose treatment with octreotide-LAR (40 mg/month) or lanreotide (120 mg/month). DESIGN: This was an open, prospective study. SUBJECTS AND METHODS: We studied 16 patients with acromegaly (nine women; aged 28-61 years). The main outcome measures were IGF-I levels, blood pressure, glucose tolerance and safety (liver function and tumor size). Pegvisomant was given at doses of 10-40 mg s.c. daily. Dose titration was performed every month by IGF-I assay. RESULTS: Three patients spontaneously stopped pegvisomant treatment after 6-9 months because of poor compliance; from the measurement of serum pegvisomant, another patient was found not to inject herself properly. After 6 months, IGF-I levels decreased by 63 +/- 19% (767.8 +/- 152.9 vs 299.8 +/- 162.9 microg/l, P < 0.0001, t-test); serum IGF-I levels normalized in 57%. After 12 months, IGF-I levels normalized in nine (75%) patients and were reduced by over 50% in another three (25%). The mean tumor volume remained stable during the study (1198 +/- 1234 vs 1196 +/- 1351 mm(3), P = 0.37): it did not change ( +/- 25% vs basal) in nine patients, increased by 39.4% and 40.8% in two and decreased by 30.8-46.5% in four. The total/high-density lipoprotein (HDL):cholesterol ratio (from 4.4 +/- 1.0 to 3.7 +/- 0.6, P = 0.0012), glucose levels (from 5.6 +/- 1.2 to 4.4 +/- 1.4 mmol/l, P = 0.026), insulin levels (from 12.4 +/- 6.7 to 8.1 +/- 3.0 mUl/l, P = 0.0023) and homeostasis model assessment (HOMA) index (from 3.4 +/- 2.1 to 1.9 +/- 1.0, P = 0.0017) decreased. CONCLUSIONS: Treatment for 12 months with pegvisomant normalized IGF-I levels, and improved cardiovascular risk parameters and insulin sensitivity in patients with acromegaly resistant to long-term, high-dose treatment with somatostatin analogs. The tolerance of treatment was good.

Acromegaly↗
PubMed2005

How robust are laboratory measures of growth hormone status?

Biochemical assessment of growth hormone (GH) status is required in both suspected GH deficiency and GH excess. GH secretion can either be measured through investigation of the pituitary or by monitoring markers that change as a consequence of GH action on its target tissues. The two most widely used and, to date, best validated biochemical parameters are immunoassay measurement of either human GH (hGH) or insulin-like growth factor (IGF)-I. The fundamental difference between measurement of hGH and IGF-I is that the first reflects GH secretion while the second reflects GH action. However, because GH secretion is pulsatile in nature, random blood sampling for determination of hGH levels is only minimally informative. Analytical methods for measuring GH and IGF-I show considerable between-method variability. Since these parameters are used in establishing diagnoses and in monitoring GH-related diseases, the endocrinologist should be aware of the specifications and limitations of the analytical methods available.

Child↗
PubMed2004

Reboxetine acutely stimulates cortisol, ACTH, growth hormone and prolactin secretion in healthy male subjects.

In this single-blind study the effects of acute oral administration of the selective noradrenaline reuptake inhibitor reboxetine on the cortisol (COR), ACTH, growth hormone (GH) and prolactin (PRL) secretion were examined in 12 healthy male volunteers. In a randomized order, the subjects received placebo or reboxetine (4 mg) at 0800 h on two different days. After insertion of an intravenous catheter, blood samples were drawn 1 hour prior to the administration of placebo or reboxetine, at time of administration, and during the time of 5 hours thereafter at periods of 30 minutes. Serum concentrations of COR, GH, and PRL as well as plasma levels of ACTH were determined in each blood sample by means of double antibody RIA, fluoroimmunoassay and chemiluminescence immunometric assay methods. The area under the curve (AUC) value was used as parameter for the COR, ACTH, GH, and PRL response. Using t-tests for paired samples, statistical analysis revealed significant stimulatory effects of reboxetine on COR, ACTH, GH, and PRL secretion, compared to placebo (mean AUC values+/-S.E.M. (a) reboxetine: COR 127893.20+/-8125.75 nmol/l x min; ACTH 2385.68+/-387.19 pmol/l x min; GH 56026.59+/-15594.87 pmol/l x min; PRL 113961.60+/-10280.44 pmol/l x min; (b) placebo: COR 83672.19+/-5225.20 nmol/l x min; ACTH 1449.83+/-190.67 pmol/l x min; GH 9308.16+/-3402.75 pmol/l x min; PRL 64663.28+/-7283.62 pmol/l x min). Mean arterial blood pressure and heart rate were significantly increased by reboxetine, too. Our results suggest that besides COR, ACTH and GH secretion, the release of PRL is also under the control of the noradrenergic systems in man.

Adrenergic Uptake Inhibitors↗
PubMed2004

Efficacy and tolerability of an individualized dosing regimen for adult growth hormone replacement therapy in comparison with fixed body weight-based dosing.

To determine whether an individualized dose titration regimen (ID) for adult GH replacement therapy would have similar efficacy and better tolerability than a fixed body weight-based dosing regimen (FD), 387 adults with GH deficiency were randomized to FD (n = 200) or ID (n = 187) for 32 wk. In FD, subjects received sequentially 4, 8, and 12 microg/kg.d GH. ID was started at 0.2 mg/d and increased by 0.2-mg/d increments, based on clinical and serum IGF-I responses, to a maximum of 0.8 mg/d. Increases (mean +/- sd) in serum IGF-I were similar in both groups (FD, 110.2 +/- 87.8 vs. ID, 99.6 +/- 77.7 microg/liter, P = 0.20) despite higher final GH doses in FD (0.70 +/- 0.32 vs. 0.54 +/- 0.22 mg/d, P < 0.001). Favorable changes in several efficacy measures were observed with no significant differences between the FD and ID groups: lean body mass increased; health-related quality of life improved; and abdominal fat mass, hip circumference, sum of skinfolds, and total and low-density lipoprotein cholesterol decreased. The decrease in fat mass was greater with FD than ID for men (-2.7 +/- 2.7 kg vs. -1.8 +/- 2.5 kg, P = 0.04) but not for women (-2.1 +/- 2.4 vs. -2.0 +/- 3.8 kg). The change in waist circumference was greater with FD than ID for women but not for men. There was a significant reduction of systolic blood pressure in ID but not in FD. The adverse event profile was similar between FD and ID except that ID had a lower occurrence of peripheral edema (9.1% vs. 16.5%, P = 0.03) and rash (1.1% vs. 5.5%, P = 0.02) than FD. In summary, the use of ID resulted in improved tolerability and similar efficacy compared with FD. We conclude that GH replacement therapy should be initiated at a low dose and titrated to a dose producing maximal benefits without adverse side effects and an IGF-I level within the age- and sex-adjusted normal range.

Adult↗
PubMed2003

The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis.

The gastrointestinal peptide hormone ghrelin stimulates appetite in rodents and humans via hypothalamic actions. We discovered expression of ghrelin in a previously uncharacterized group of neurons adjacent to the third ventricle between the dorsal, ventral, paraventricular, and arcuate hypothalamic nuclei. These neurons send efferents onto key hypothalamic circuits, including those producing neuropeptide Y (NPY), Agouti-related protein (AGRP), proopiomelanocortin (POMC) products, and corticotropin-releasing hormone (CRH). Within the hypothalamus, ghrelin bound mostly on presynaptic terminals of NPY neurons. Using electrophysiological recordings, we found that ghrelin stimulated the activity of arcuate NPY neurons and mimicked the effect of NPY in the paraventricular nucleus of the hypothalamus (PVH). We propose that at these sites, release of ghrelin may stimulate the release of orexigenic peptides and neurotransmitters, thus representing a novel regulatory circuit controlling energy homeostasis.

Agouti-Related Protein↗
PubMed2003

Regulation of growth-hormone-receptor gene expression by growth hormone and pegvisomant in human mesangial cells.

BACKGROUND: Mice transgenic for growth hormone develop mesangial proliferation, glomerular hypertrophy, and progressive glomerular sclerosis suggesting that the growth hormone-insulin-like growth factor I (IGF-I) pathway plays an important role. Therefore, we studied the impact of variable concentrations of 22 kD, 20 kD growth hormone, as well as of the growth hormone receptor antagonist pegvisomant (B2036-PEG), on both the growth hormone receptor (GHR/GHBP) gene expression and growth hormone binding protein (GHBP) formation in a human glomerular mesangial cell line. Further, the impact on collagen, IGF-I and IGF binding protein-1 (IGFBP-1) formation was studied. METHODS: In order to assess transcription, quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used. RESULTS: Physiologic doses of 22 kD or 20 kD growth hormone caused a dose-dependent and significant (P < 0.01) up-regulation of GHR/GHBP gene transcription, whereas supraphysiologic doses (50 and 500 ng/mL) resulted in down-regulation (P < 0.001). Whenever pegvisomant was used, there was no increase in GHR/GHBP expression. These data were confirmed using run-on experiments. Further, the assessment of GHBP presented a constant, dose-dependent increase, which was completely abolished in the experiments where pegvisomant was used. CONCLUSION: We present data showing that growth hormone has a direct impact on GHR/GHPB gene transcription and that pegvisomant is a potent growth hormone receptor antagonist in human mesangial cells. In addition, although the GHR/GHBP gene transcription is down-regulated by supraphysiologic growth hormone concentrations, this effect was not found when GHBP levels were measured. This finding may reflect a self-inhibitory effect of growth hormone on the level of GHR/GHBP gene transcription, which does not involve the regulation of the shedding of GHBP and may, therefore, be of physiologic interest.

Cells, Cultured↗
PubMed2003

A new nonisotopic, highly sensitive assay for the measurement of human placental growth hormone: development and clinical implications.

Human placental GH (hGH-V) is a variant of pituitary hGH (hGH-N) synthesized and secreted by syncytiotrophoblasts during pregnancy. It differs from hGH-V by only 13 amino acid residues, which makes difficult a specific measurement of hGH-V without interference from hGH-N. To overcome the analytical difficulties, we produced new high affinity monoclonal antibodies specific for hGH-V. Precise screening and epitope mapping allowed identification of a pair of monoclonal antibodies suitable to establish a highly sensitive assay for hGH-V measurement. In a prospective, longitudinal study involving 84 normal pregnancies, we measured maternal concentrations of hGH-V, leptin, IGF-I, and cord blood IGF-I. hGH-V was detectable as early as gestational week (GW) 7. Mean concentrations of hGH-V increased from 0.9 +/- 0.5 microg/liter (GW 7-13) to 2.8 +/- 0.9 microg/liter (GW 18-22), 7.3 +/- 2.6 microg/liter (GW 28-32), and 13.0 +/- 9.6 (GW 37-41). A negative correlation was found between prepregnancy body mass index and hGH-V concentrations from GW 28 onward. Peak hGH-V levels occurred at wk 36.5 +/- 2.6 and were significantly lower in obese (P = 0.029) and higher in underweight (P = 0.035) mothers compared with those in mothers of normal weight. The increase in hGH-V between GW 18-22 and GW 28-32 was negatively correlated to the increase in maternal leptin during this period (P = 0.027). Maternal IGF-I concentrations were correlated to those of hGH-V from GW 18 onward (P = 0.039). The strongest correlation was found at GW 28-32 (P = 0.001). Furthermore, maternal hGH-V concentrations in late pregnancy correlated with cord blood IGF-I (P = 0.025) and size of the newborn (P = 0.017). These results, obtained by a new, highly sensitive hGH-V-specific immunoassay, highlight the importance of maternal hGH-V in the regulation of maternal and fetal IGF-I. In addition, the results indicate that maternal weight has a major impact on circulating concentrations of hGH-V.

Animals↗
PubMed2003

Heterozygous nonsense mutation in exon 3 of the growth hormone receptor (GHR) in severe GH insensitivity (Laron syndrome) and the issue of the origin and function of the GHRd3 isoform.

Mutations in the GH receptor gene (GHR) cause congenital GH insensitivity, a genetic disorder characterized by severe growth retardation associated with high serum concentration of GH and low serum levels of IGF-I. Molecular defects have been identified in all GHR-coding exons, except exon 3, a sequence that encodes part of the extracellular domain of the receptor. In humans, GHR transcripts exist in two isoforms differing by the retention (GHRfl) or exclusion (GHRd3) of this particular exon. As shown recently, such a dimorphic expression pattern, of unknown significance, could result from a retrovirus-mediated deletion event involving exon 3. This model for the generation of those two isoforms, however, leaves open the possibility that GHRd3 transcripts also arise from GHRfl alleles through alternative splicing. Here we report the identification of the first mutation in exon 3 of the GHR (W16X) in a patient with GH insensitivity and who also carries another nonsense mutation in exon 4. Intrafamilial correlation analyses of genotypes (presence of normal or mutant GHRfl and/or GHRd3 alleles), GHR expression patterns, and phenotypes provided direct evidence against an alternative splicing of exon 3. In particular, this exon was retained into transcripts originating from the GHRfl-W16X allele in both the patient and his mother. These observations, given the normal phenotype of the heterozygous parents, revealed also that a single copy of either GHRfl or GHRd3 is sufficient for normal growth.

Alternative Splicing↗
PubMed2003

Decreased quality of life in adult patients with growth hormone deficiency compared with general populations using the new, validated, self-weighted questionnaire, questions on life satisfaction hypopituitarism module.

To develop reference ranges for the Questions on Life Satisfaction Hypopituitarism Module (QLS-H), a new quality of life questionnaire for patients with hypopituitarism, data from 8177 adults were collected in France, Germany, Italy, The Netherlands, Spain, the United Kingdom, and the United States QLS-H scores declined with age, were lower in females than males, and differed significantly among countries. From these reference ranges we derived equations for z-scores, which adjust for age, gender, and country. QLS-H results from 957 adults with GH deficiency (GHD) participating in clinical trials were analyzed. At baseline, QLS-H scores were lower in females and differed significantly among countries. QLS-H scores significantly increased after GH treatment (6-8 months), but differences by country persisted. Calculating z-scores for patients eliminated all gender and most country differences. Pooled z-scores (mean +/- SD) from all patients increased from -0.99 +/- 1.39 at baseline to -0.14 +/- 1.30 after GH treatment. Quality of life assessment in adults with GHD requires the use of z-scores to correct for age, gender, and country differences. This approach allows pooling of data from different cohorts and comparison with general populations. QLS-H scores in adults with GHD were significantly decreased at baseline and were almost normalized after 6-8 months of GH therapy.

Adult↗
PubMed2003

Optimizing control of acromegaly: integrating a growth hormone receptor antagonist into the treatment algorithm.

Acromegaly is associated with significant morbidities and a 2- to 3-fold increase in mortality because of the excessive metabolic action of GH and IGF-I, a marker of GH output. Reductions in morbidity correspond with decreases in IGF-I, and mortality is lowered following normalization of IGF-I or GH levels. Therefore, this has become an important end point. Current guidelines for the treatment of acromegaly have not considered recent advances in medical therapy, in particular, the place of pegvisomant, a GH receptor antagonist. Treatment goals include normalizing biochemical markers, controlling tumor mass, preserving pituitary function, and relieving signs and symptoms. Surgery reduces tumor volume and is considered first-line therapy. Radiation reduces tumor volume and GH and IGF-I levels, but the onset of action is slow and hypopituitarism typically develops. Therefore, pharmacotherapy is often used following surgery or as first-line therapy for nonresectable tumors. Dopamine agonists can be considered in patients exhibiting minimal disease or those with GH-prolactin-cosecreting tumors but will not achieve hormone normalization in most patients. Somatostatin analogs effectively suppress GH and IGF-I in most patients, but intolerance (e.g. diarrhea, cramping, gallstones) can occur. Pegvisomant, the newest therapeutic option, blocks GH action at peripheral receptors, normalizes IGF-I levels, reduces signs and symptoms, and corrects metabolic defects. Pegvisomant does not appear to affect tumor size and has few adverse effects. Pegvisomant is the most effective drug treatment for acromegaly in normalizing IGF-I and producing a clinical response; it is the preferred agent in patients resistant to or intolerant of somatostatin analogs.

Acromegaly↗
PubMed2003

Decreasing resistance in the maternal uterine and peripheral arterial system is apparently unrelated to plasma and urinary levels of nitrite/nitrate and cyclic-guanosinmonophosohate during the course of normal pregnancies.

AIMS: The aim of the presented study was to clarify the relationship between the pulsatility index of the uterine arteries and the maternal cubital artery and peripheral concentrations of the metabolites of nitric oxide (NO) and its second messenger cyclic guanosinmonophophate (cGMP) during the normal course of pregnancy and postpartum. METHODS: 49 uncomplicated pregnancies were investigated every 4-6 weeks until delivery, 29 of them were additionally investigated postpartum. Paralleling each Doppler sonographic investigation maternal blood and urine samples were taken. The measurements of nitrite/nitrate and cGMP were performed with a colorimetric and radio immuno assay. We demonstrate a significant decrease of the PI of the uterine arteries and of the cubital artery with inverse correlation to advancing gestational age. RESULTS: The concentrations of nitrite/nitrate and cGMP remain stable during gestation and do not correlate to the PI of the uterine and cubital artery. Postpartum a re-increase in the uterine and peripheral resistance can be shown. The concentrations of urinary cGMP and nitrite/nitrate as well as plasma cGMP remain unchanged, whereas plasma nitrite/nitrate decreases postpartum. CONCLUSIONS: The status of NO biosyntheses in normal pregnancy remains controversial. We hypothesize further systemically acting mediators which contribute to the decreasing vascular resistance.

Adult↗
PubMed2002

Evaluation of a salivary based combined dexamethasone/CRH test in patients with major depression.

The combined dexamethasone/corticotropin releasing hormone (Dex/CRH) test is one of the most reliable neuroendocrine function tests for investigation of hypothalamic-pituitary-adrenocortical (HPA) system dysregulation in depression. Persistent high HPA system activity reflected by an enhanced cortisol secretion during the Dex/CRH test after successful antidepressant treatment is correlated with an enhanced risk for relapse in remitted depressives. Thus, the Dex/CRH test might be a useful neuroendocrinological tool for treatment monitoring. However, the performance of the test requiring multiple blood samplings renders this test difficult for routine clinical use. Thus, a simplified test procedure using a saliva based test without the necessity of multiple blood samplings would be desirable.Therefore, we compared matched saliva and serum probes of Dex/CRH tests of 73 depressed patients who underwent a total of 157 tests. Both saliva and serum cortisol concentrations showed a significant stimulation pattern during the test and were highly correlated. This correlation was not influenced by either antidepressive treatment. In patients with high cortisol secretion patterns during the Dex/CRH test there was a decrease in HPA system activity after successful antidepressant treatment that was reflected by both the saliva and the serum Dex/CRH test.Thus, the saliva based combined Dex/CRH test appears to be a suitable tool for monitoring HPA system activity during the course of depressive illness. The easier performance of the saliva Dex/CRH test in comparison to the standard test procedure for both patients and hospital staff opens the door for routine clinical use of the Dex/CRH test for treatment monitoring and estimation of relapse risk.

Adult↗
PubMed2002

Human growth hormone replacement in adult hypopituitary patients: long-term effects on body composition and lipid status--3-year results from the HypoCCS Database.

The Hypopituitary Control and Complications Study is an international surveillance study evaluating efficacy and safety of GH therapy of adult GH-deficient patients in clinical practice. The present report examined baseline data from 1,123 adult onset (AO) and 362 childhood onset (CO) patients, as well as efficacy in 242 patients who had completed 3 yr of GH treatment. At study entry, mean height, body mass index, waist to hip ratio, and lean body mass were significantly (P < 0.001 for each) lower in CO compared with AO patients. After 3 yr on GH, lean body mass was significantly increased in AO males and females and CO males but not CO females, whereas fat mass was significantly decreased in AO males only. Serum total cholesterol was decreased in females (-0.32 +/- 1.00 mmol/liter; P = 0.045) and males (-0.36 +/- 0.96 mmol/liter; P = 0.004). High-density lipoprotein (HDL) cholesterol was increased for females (0.10 +/- 0.26 mmol/liter; P = 0.026) and males (0.10 +/- 0.34 mmol/liter; P = 0.022). The low-density lipoprotein/HDL ratio was decreased in AO males (-0.93 +/- 2.00; P = 0.003), AO females (-0.65 +/- 0.74; P < 0.001), and CO females (-0.69 +/- 0.76; P = 0.038), but the decrease in CO males was not significant (-0.84 +/- 2.85; P = 0.273). In AO patients, lean body mass increase from baseline was greatest in the those younger than 40 yr old, less but still significant in the middle group (40-60 yr) and unchanged in older (>60 yr) patients; conversely, decreases in the low-density lipoprotein/HDL ratio were small and not significant in the younger patients but greater and significant in the middle and older age groups. During the 3-yr treatment, 114 (7.7%) patients discontinued, including 9 (0.6%) for tumor recurrences, 9 (0.6%) for neoplasia, and 9 (0.6%) for side effects. Therefore, these observational data showed significant long-term efficacy of adult GH replacement therapy on body composition and lipid profiles and indicate that age is an important predictor of response.

Adult↗
PubMed2002

Quantification of the soluble leptin receptor in human blood by ligand-mediated immunofunctional assay.

Panels of monoclonal antibodies (mAbs) were raised against recombinant human leptin and the recombinant human soluble leptin receptor. Using these mAbs, we established a ligand-mediated immunofunctional assay (LIFA) to quantify concentrations of the soluble leptin receptor, which has been shown to be a major binding protein for leptin in human serum. In performing the assay, a monoclonal antibody (mAb 2H6) against the soluble leptin receptor, which binds an epitope outside the leptin-binding site and equally recognizes both, free and leptin-occupied soluble leptin receptor, is used to capture the soluble leptin receptor on a microtiter plate. Recombinant human leptin is added to saturate all binding sites, and a biotinylated anti-leptin mAb (4D3) detects the amount of leptin (endogenous and exogenous) bound to the soluble leptin receptor. The same procedure, but without adding exogenous leptin, allows for measurement of the circulating endogenous leptin/soluble leptin receptor complexes. The LIFA assay has a linear working range of 0.5-200 microg/liter, intra- and interassay coefficients of variation ranged from 3.2-6.3% and from 5.2-7.9%, respectively. The assay has a linearity of 102.2 +/- 5.2% (mean +/- SD) and a recovery of 100.7 +/- 6.9%. Size-exclusion chromatography revealed that the assay measures a protein with a main peak eluted at 340 kDa. The soluble leptin receptor concentration (63.3 +/- 22.8 microg/liter (mean +/- SD), range 17.9-129.2 microg/liter, n = 43) in normal subjects (body mass index = 22.3 +/- 2.3 kg/m(2)) was not different from the concentration (54.4 +/- 19.8 microg/liter, range 23.7-104.8 microg/liter, n = 34, P > 0.05) found in obese subjects (body mass index = 40.9 +/- 15.7 kg/m(2)). However, the percentage of the total soluble leptin receptor complexed with endogenous leptin was significantly higher in obese subjects, compared with normal subjects (74.9% +/- 23.5% vs. 33.1% +/- 19.5%, P < 0.001). Higher serum leptin levels in obese subjects (38.4 +/- 23.7 microg/liter vs. 7.8 +/- 5.5 microg/liter in normal subjects, P < 0.001) together with comparable soluble leptin receptor levels result in a lower proportion of leptin bound to the soluble leptin receptor in obese subjects (19.3% +/- 19.4%, range 4.9-97.2%) than in normal subjects (39.0% +/- 22.5%, range 15.3-96.5%, P < 0.001). The development of this LIFA for the rapid and accurate quantification of total soluble leptin receptor and circulating leptin/soluble leptin receptor complexes provides a valuable tool for the further understanding of the role of leptin and its soluble receptor in health and disease.

Adult↗