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- Andersson, Björn, 1977, et al.
(author)
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Protein profiling identified dissociations between growth hormone-mediated longitudinal growth and bone mineralization in short prepubertal children
- 2011
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In: Journal of Proteomics. - : Elsevier BV. - 1876-7737 .- 1874-3919. ; 74:1
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Journal article (peer-reviewed)abstract
- Growth hormone (GH) promotes longitudinal growth and bone mineralization. In this study, a proteomic approach was used to analyze the association between serum protein expression pattern and height-adjusted bone mineralization in short prepubertal children receiving GH treatment. Patterns of protein expression were compared with those associated with longitudinal bone growth. Specific protein expression patterns associated with changes in height-adjusted bone mineralization in response to GH treatment were identified. Out of the 37 peaks found in significant regression models, 27 were uniquely present in models correlated with changes in bone mineralization and 7 peaks were uniquely present in models correlated with changes in height. The peaks identified corresponded to apolipoproteins, transthyretin, serum amyloid A4 and hemoglobin beta. We conclude that a proteomic approach could be used to identify specific protein expression patterns associated with bone mineralization in response to GH treatment and that height-adjusted bone mineralization and longitudinal bone growth are regulated partly by the same and partly by different mechanisms. Protein isoforms with different post-translational modifications might be of importance in the regulation of these processes. However, further validation is needed to assess the clinical significance of the results.
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| 2. |
- Decker, Ralph, 1968, et al.
(author)
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Metabolic outcome of GH treatment in prepubertal short children with and without classical GH deficiency
- 2010
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In: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 73:3
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Journal article (peer-reviewed)abstract
- Context: Few studies have evaluated the metabolic outcomes of growth hormone (GH) treatment in idiopathic short stature (ISS). Moreover, children with ISS appear to need higher GH doses than children with GH deficiency (GHD) to achieve the same amount of growth, and may therefore be at increased risk of adverse events during treatment. The individualized approach using prediction models for estimation of GH responsiveness, on the other hand, has the advantage of narrowing the range of growth response, avoiding too low or high GH doses. Design: Short prepubertal children with either isolated GHD (39) or ISS (89) participated in a 2-year randomized trial of either individualized GH treatment with six different GH doses (range, 17-100 mug/kg/day) or a standard dose (43 mug/kg/day). Objective: To evaluate if individualized GH treatment reduced the variance of the metabolic measures as shown for growth response, and to compare changes in metabolic variables in children with ISS and GHD. Hypothesis: Individualized GH dose reduces the range of metabolic outcomes, and metabolic outcomes are similar in children with ISS and GHD. Results: We observed a narrower variation for fasting insulin (-34.2%) and for HOMA (-38.9%) after two years of individualized GH treatment in comparison to standard GH dose treatment. Similar metabolic changes were seen in ISS and GHD. Delta (Delta) height SDS correlated with Deltainsulin-like growth factor I (IGF-I), Deltaleptin and Deltabody composition. Principal component analysis identified an anabolic and a lipolytic component. Anabolic variables [Deltalean body mass (LBM) SDS and DeltaIGF-I SDS] clustered together and correlated strongly with Deltaheight SDS and GH dose, whereas lipolytic variables [Deltafat mass SDS and Deltaleptin] were clustered separately from anabolic variables. Regression analysis showed GH dose-dependency in ISS, and to a lesser degree in GHD, for DeltaLBM SDS and Deltaheight SDS, but not for changes in fat mass. Conclusions: Individualized GH dosing during catch-up growth reduces the variance in insulin and HOMA and results in equal metabolic responses irrespective of the diagnosis of GHD or ISS.
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| 3. |
- Decker, Ralph, 1968, et al.
(author)
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Protein markers predict body composition during growth hormone (GH) treatment in short prepubertal children.
- 2013
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In: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 79:5, s. 675-82
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Journal article (peer-reviewed)abstract
- OBJECTIVE: A high-throughput pharmaco-proteomic approach has previously been successfully used to identify lipoprotein biomarkers related to changes in longitudinal growth and bone mass in response to growth hormone (GH) treatment. The aim of this study was to identify protein markers involved in the diverse anabolic and lipolytic remodelling of body composition during GH treatment. DESIGN, PATIENTS AND MEASUREMENTS: The study population consisted of 128 prepubertal children receiving GH treatment. Thirty-nine were short as a result of GH deficiency and 89 had idiopathic short stature (ISS). Serum protein expression profiles at study start and after one year of GH treatment were analysed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Body composition was analysed by dual-energy X-ray absorptiometry (DXA), reliably estimating muscle mass from appendicular (arms and legs) lean soft tissue mass (LST). DXA was also used to estimate appendicular bone mineral content (BMC) and fat mass for the total body. RESULTS: Specific protein expression patterns associated with GH response in different body compartments were identified. Among identified proteins different isoforms of nutrition markers such as apolipoproteins (Apo) were recognized; Apo C-I, Apo A-II, serum amyloid A4 (SAA4) and transthyretin (TTR). In addition, unidentified peaks were associated with GH effects on specific body compartments. CONCLUSIONS: Our results suggest that unique protein markers are associated with remodelling of different body compartments during GH treatment, which in the future might be useful to optimize GH treatment not only with regard to longitudinal growth. © 2013 Blackwell Publishing Ltd.
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| 4. |
- Hellgren, Gunnel, 1961, et al.
(author)
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Protein expression profiling supports ‘the biphasic model’ theory of bone mineralization in response to GH treatment in short prepubertal children
- 2010
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In: Hormone Research Paediatr. ; 74:Suppl 3, s. 100-101
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Conference paper (peer-reviewed)abstract
- According ’the biphasic model’ of GH action in bone it has been suggested that, in the initial phase after the start of treatment, GH increases bone resorption, followed by a phase of increased bone formation. The aim of this study was to use a proteomic approach to identify serum protein markers associated with GH-dependent bone mineralization the first two years of GH treatment. The study group consisted of 128 short GH-treated prepubertal children; 39 GHD and 89 idiopathic short stature (ISS), included in a clinical trial. Serum protein expression profiles were analyzed using SELDI-TOF on 3 different ProteinChip surfaces. Peak data were analyzed using regression methods and random permutation tests with bone mineral content (BMC) as output variable, measured by dual energy x-ray absorptiometry (DEXA). To eliminate height influence of the results BMC was adjusted for height (BMCHA). BMCHA decreased during the 1st yr of treatment in both the GHD and the ISS groups, and then increased to a value higher than at start of treatment during the 2nd yr. Peak data analyses of the GHD group supported the ’the biphasic model’ theory. Different groups of peaks correlated with changes in BMCHA during the 1st yr compared to the 2nd yr. At start of treatment no regression models correlated with 1st yr delta BMCHA, whereas a group of 5 peaks correlated with the 2nd yr delta BMCHA (p=0.036). Changes in protein expression pattern 0 – 1 yr correlated with the 1st (p=0.016) and the 2nd (p=0.006) yr delta BMCHA. There was no overlap of peaks between the regression models correlated with the 1st and the 2nd yr delta BMCHA, respectively. Work is in progress to identify specific proteins of interest. We conclude that these results could be useful to explain the biology behind the different phases of bone metabolism in response to GH treatment. Peaks so far identified, indicate that different forms of monomeric and dimeric apolipoprotein A-2 probably are involved in these processes.
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