scholarly journals The proteomic signature of recombinant Growth Hormone in recreational athletes

2021 ◽  
Author(s):  
Max Esefeld ◽  
Antoni Pastor ◽  
Rafael de la Torre ◽  
Osquel Barroso ◽  
Reid Aikin ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Serum Proteins ◽  
Human Growth ◽  
Biological Processes ◽  
Protein Markers ◽  
Serum Samples ◽  
Recombinant Growth Hormone ◽  
Recreational Athletes ◽  
Protein Levels ◽  
New Biomarkers

Abstract Objectives Administration of human growth hormone (hGH) is prohibited in competitive sport and its detection in an athlete’s sample triggers an adverse analytical finding. However, the biological processes that are modulated by recombinant hGH are not well characterized and associated blood serum proteins may constitute new biomarkers for hGH misuse. Methods Thirty-five recreational athletes were enrolled in a study to investigate the time- and dose-dependent response of serum protein levels to recombinant hGH administration. Participants were randomized into four groups, receiving one of three different doses of recombinant hGH or a placebo. Bio samples were collected at 22 time points over a period of 13 weeks, starting four weeks prior to treatment, three weeks of treatment, and six weeks’ follow-up. A total of 749 serum samples was analyzed for 1,305 protein markers using the SOMAscan® proteomics platform. Results We identified 66 proteins that significantly associated with recombinant hGH administration and dosage, including well known hGH targets, such as IGF1, but also previously unknown hGH-related proteins (e.g.: protease inhibitors, WFIKKN1, and chemokines, CCL2). Network analysis revealed changes in specific biological pathways, mainly related to the immune system and glucose metabolism. Conclusion Our analysis suggests that hGH administration is impacting biological processes more strongly than previously acknowledged. Some of the proteins were dysregulated even after hGH treatment and could potentially be developed into biomarkers for hGH misuse. Moreover, our findings suggest new roles for hGH associated proteins in the etiology of hGH related diseases and may indicate new risks that may be associated with hGH misuse.

Time-resolved immunofluorometric assay of human growth hormone

1993 ◽  
Vol 39 (8) ◽  
pp. 1620-1625 ◽  
Author(s):  
K Albertsson-Wikland ◽  
C Jansson ◽  
S Rosberg ◽  
A Novamo
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Polyclonal Antibodies ◽  
Human Growth ◽  
Immunoradiometric Assay ◽  
Serum Samples ◽  
Time Resolved ◽  
Counting Time ◽  
Pediatric Use ◽  
The Eu

Abstract We describe a time-resolved immunofluorometric assay (trIFMA) for human growth hormone (hGH), in which monoclonal antibody (mAb)-coated microtiter strip wells and a europium (Eu) chelate-labeled mAb are used. We compare the new trIFMA, in which two mAbs are used, with an immunoradiometric assay (IRMA) in which polyclonal antibodies are used. Serum samples (n = 185) from 36 children with various diagnoses were analyzed. In addition, 24-h profile samples (72 per child) from 39 children were analyzed. The trIFMA was more sensitive (detection limit, 0.03 mIU/L) than existing IRMAs. Both the intra- and interassay CVs were < or = 10.6% for hGH concentrations between 1 and 100 mIU/L. The trIFMA is technically simple and rapid, requires no centrifugation or separation reagent, and has a counting time of only 1 s per sample. In addition, the Eu label is nontoxic, presents no waste-disposal problems, and has a long shelf-life. Finally, the assay requires only small volumes of serum (25 muL), which is of considerable importance in pediatric use. The mAbs used for the trIFMA selectively bind the 22-kDa form of hGH, with the result that the assay detects about 80% of the amount detected by the polyclonal IRMA.

scholarly journals Gaps in the Traceability Chain of Human Growth Hormone Measurements

2013 ◽  
Vol 59 (7) ◽  
pp. 1074-1082 ◽  
Author(s):  
Sébastien Boulo ◽  
Katja Hanisch ◽  
Martin Bidlingmaier ◽  
Cristian-Gabriel Arsene ◽  
Mauro Panteghini ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Higher Order ◽  
Serum Samples ◽  
Traceability Chain ◽  
Eu Directive ◽  
In Vitro Diagnostic ◽  
Relative Differences

BACKGROUND Human growth hormone (hGH) is measured for the diagnosis of secretion disorders. These measurements fall under the EU Directive 98/79/EC on in vitro diagnostic medical devices requiring traceability of commercial calibrator values to higher-order reference materials or procedures (Off J Eur Communities 1998 Dec 7;L 331:1–37). External quality assessment schemes show large discrepancies between results from different methods, even though most methods provide results traceable to the recommended International Standard (IS 98/574). The aim of this study was to investigate possible causes for these discrepancies. METHODS We investigated the commutability and recovery of hGH in reconstituted IS 98/574. We tested different reconstitution protocols and used 4 different serum matrices for spiking. These IS preparations were measured together with serum samples. We quantified hGH by 5 different methods in 4 different laboratories. RESULTS Results from the different methods correlated well for the serum samples. Mean discrepancies between results from different methods were ≤20%. None of the IS preparations was commutable for all the method comparisons. The recovery of hGH in preparations of IS 98/574 depended on the reconstitution protocol (>10-fold differences) and BACKGROUND matrix (relative differences ≤17% for different serum matrices). CONCLUSIONS The use of different protocols for reconstitution and spiking of hGH reference preparations affects quantification by immunoassays, potentially leading to a bias between commercial methods, despite the use of calibrators with values claimed to be traceable to the same higher-order reference material.

scholarly journals Administration of bovine, porcine and equine growth hormone to the horse: effect on insulin-like growth factor-I and selected IGF binding proteins

2001 ◽  
Vol 171 (1) ◽  
pp. 163-171 ◽  
Author(s):  
SS De Kock ◽  
JP Rodgers ◽  
BC Swanepoel ◽  
AJ Guthrie
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Protein Markers ◽  
Recombinant Growth Hormone ◽  
Igf Binding Proteins ◽  
Thoroughbred Horses ◽  
Igf I ◽  
Igf Binding ◽  
Time Required

This study investigated the biochemical effects of administration of three types of recombinant growth hormone (GH; somatotropin) to the Thoroughbred horse. Equine or bovine or porcine GH was administered at a recommended dosage to 3-5-year old Thoroughbred geldings, for up to 21 days. It was shown that, in addition to equine GH, bovine and porcine GH were active in the horse; however, porcine GH caused injection-site reactions that were so serious that administration had to be terminated. The concentrations of a range of GH-related serum protein markers were determined before, during and after the administration period. Because of the short half-life of GH itself, the objective was to identify GH-related markers that showed changes in concentration and which could be used as indicators of the abuse of these hormones. Among the possible markers identified, serum total insulin-like growth factor (IGF)-I was shown to be the most promising, increasing to 270% of the basal concentration for equine GH administration. After GH administration, IGF-I took longer to attain baseline concentrations than the time required for GH concentrations to recover to normal. The concentration obtained from the administration significantly exceeded natural concentrations for IGF-I, as was determined from a population of more than 2000 Thoroughbred horses in three continents. The concentrations of serum free IGF-I and IGF binding protein 3 (IGFBP-3) were also shown to be significantly affected by equine and bovine GH.

scholarly journals High-Sensitivity Chemiluminescence Immunoassays for Detection of Growth Hormone Doping in Sports

2009 ◽  
Vol 55 (3) ◽  
pp. 445-453 ◽  
Author(s):  
Martin Bidlingmaier ◽  
Jennifer Suhr ◽  
Andrea Ernst ◽  
Zida Wu ◽  
Alexandra Keller ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Single Injection ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
High Sensitivity ◽  
High Dose ◽  
Recreational Athletes ◽  
Before And After ◽  
Sandwich Type ◽  
Preferential Recognition

Abstract Background: Recombinant human growth hormone (rhGH) is abused in sports, but adequate routine doping tests are lacking. Analysis of serum hGH isoform composition has been shown to be effective in detecting rhGH doping. We developed and validated selective immunoassays for isoform analysis with potential utility for screening and confirmation in doping tests. Methods: Monoclonal antibodies with preference for pituitary hGH (phGH) or rhGH were used to establish 2 pairs of sandwich-type chemiluminescence assays with differential recognition of rhGH (recA and recB) and phGH (pitA and pitB). We analyzed specimens from volunteers before and after administration of rhGH and calculated ratios between the respective rec- and pit-assay results. Results: Functional sensitivities were <0.05 μg/L, with intra- and interassay imprecision ≤8.4% and ≤13.7%, respectively. In 2 independent cohorts of healthy subjects, rec/pit ratios (median range) were 0.84 (0.09–1.32)/0.81 (0.27–1.21) (recA/pitA) and 0.68 (0.08–1.20)/0.80 (0.25–1.36) (recB/pitB), with no sex difference. In 20 recreational athletes, ratios (median SD) increased after a single injection of rhGH, reaching 350% (73%) (recA/pitA) and 400% (93%) (recB/pitB) of baseline ratios. At a moderate dose (0.033 mg/kg), mean recA/pitA and recB/pitB ratios remained significantly increased for 18 h (men) and 26 h (women). After high-dose rhGH (0.083 mg/kg), mean rec/pit ratios remained increased for 32 h (recA/pitA) and 34 h (recB/pitB) in men and were still increased after 36 h in women. Conclusions: Using sensitive chemiluminescence assays with preferential recognition of phGH or rhGH, detection of a single injection of rhGH was possible for up to 36 h.

Application of the Athlete Biological Passport approach to the detection of growth hormone doping

2021 ◽  
Author(s):  
Tristan Equey ◽  
Antoni Pastor ◽  
Rafael de la Torre Fornell ◽  
Andreas Thomas ◽  
Sylvain Giraud ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Outcome Measure ◽  
High Dose ◽  
Serum Samples ◽  
Open Label ◽  
Recreational Athletes ◽  
Biological Passport ◽  
Individual Profiles ◽  
Cessation Of Treatment ◽  
Different Doses

Abstract Context Because of its anabolic and lipolytic properties, growth hormone (GH) use is prohibited in sport. Two methods based on population derived decision limits are currently used to detect human GH (hGH) abuse: the hGH Biomarkers Test and the Isoforms Differential Immunoassay. Objective Test the hypothesis that longitudinal profiling of hGH biomarkers through application of the Athlete Biological Passport (ABP) has the potential to flag hGH abuse. Design IGF-1 and P-III-NP distributions were obtained from 7 years of anti-doping data and applied as priors to analyse individual profiles from an hGH administration study in recreational athletes. Setting Academic and anti-doping laboratories. Elite (n=11,455) and recreational athletes (n=35). Intervention(s) An open-label, randomized, single site, placebo-controlled administration study was carried out with individuals randomly assigned to 4 arms: placebo, or 3 different doses of recombinant hGH. Main Outcome Measure(s) Serum samples were analyzed for IGF-1, P-III-NP, and hGH isoforms and the performance of a longitudinal, ABP-based approach was evaluated. Results An ABP-based approach set at a 99% specificity level flagged 20/27 individuals receiving hGH treatment, including 17/27 individuals after cessation of the treatment. ABP sensitivity ranged from 12.5-71.4 % across the hGH concentrations tested following 7 days of treatment, peaking at 57.1-100 % after 21 days of treatment, and was maintained between 37.5-71.4 % for the low and high dose groups one week after cessation of treatment. Conclusions These findings demonstrate that longitudinal profiling of hGH biomarkers can provide suitable performance characteristics for use in anti-doping programs.

Determinants of Final Height in Patients Born Small for Gestational Age Treated with Recombinant Growth Hormone

2021 ◽  
pp. 1-11
Author(s):  
Elodie Adler ◽  
Anne-Sophie Lambert ◽  
Claire Bouvattier ◽  
Cécile Thomas-Teinturier ◽  
Anya Rothenbuhler ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Final Height ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Birth Length ◽  
Pediatric Endocrinology ◽  
Gnrh Analog ◽  
Recombinant Growth Hormone

<b><i>Introduction:</i></b> About 8% of children born small for gestational age (SGA) do not reach a final height within the normal range. Recombinant human growth hormone (rhGH) has been shown to be effective in increasing the final height in children born SGA. Our objective was to identify predictive factors of final height in children born SGA treated with rhGH. <b><i>Materials and Methods:</i></b> In this retrospective study, conducted in a tertiary pediatric endocrinology referral center, we recruited all patients born SGA (defined as birth length or weight &#x3c;10th percentile) treated with rhGH for more than 12 months for whom final height data were available. Some patients had received gonadotropin-releasing hormone (GnRH) analog therapy. <b><i>Results:</i></b> We included 252 patients with an average birth length of −2.0 ± 0.7 SD and birth weight of −1.7 ± 1.0 SD. After 4.6 ± 2.8 years of rhGH treatment, their height increased from −2.2 ± 0.9 SD to −1.5 ± 0.9 SD. In multivariate analysis, we identified 8 factors that predict 46% of the final height, namely, cause of SGA (<i>p</i> &#x3c; 0.0001), GnRH analog therapy &#x3e;2 years (<i>p</i> = 0.006), birth length (<i>p</i> &#x3c; 0.02), height at the start of rhGH (<i>p</i> &#x3c; 0.0001), IGF-1 level at the start of rhGH (<i>p</i> = 0.0002), growth velocity during the 1st year of treatment (<i>p</i> = 0.0002), and age and height at the onset of puberty (<i>p</i> &#x3c; 0.0001, <i>p</i> = 0.0007, respectively). <b><i>Conclusion:</i></b> In this large cohort of SGA patients who had reached their final height, we were able to confirm that growth hormone increases final height in short SGA children. In addition, we identified several factors associated with a better response to growth hormone treatment.

scholarly journals Stimulation of monocyte chemotaxis by human growth hormone and its deactivation by somatostatin

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 954-960 ◽  
Author(s):  
CJ Wiedermann ◽  
N Reinisch ◽  
H Braunsteiner
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Inhibitory Effect ◽  
Boyden Chamber ◽  
Recombinant Growth Hormone ◽  
Monocyte Chemotaxis ◽  
Long Acting

Monocyte infiltration occurs early in the course of inflammation and is a prerequisite for optimal repair of tissue damage. In this study, human recombinant growth hormone was shown to be a potent chemoattractant for human monocytes, inducing migration at picomolar concentrations of recombinant human growth hormone. Chemotaxis of monocytes was measured in vitro by a modified Boyden chamber assay using nitrocellulose micropore filters and measuring microscopically the migration depth of the leading front of monocytes. Somatostatin, which inhibits the release of growth hormone, and its long-acting analogue, octreotide, also stimulated chemotaxis of monocytes; however, the effective peptide concentration was in the micromolar range. When tested for chemotaxis in combination or in experiments using pretreatment with somatostatin and washing of treated cells, somatostatin significantly antagonized the chemotactic responses of monocytes to growth hormone. The inhibitory effect on growth hormone- stimulated chemotaxis was dose dependent and occurred at concentrations severalfold lower than the chemotactically active concentration of somatostatin. Combinations of growth hormone with interferon or substance P also deactivated the chemotactic responses. These observations suggest that human growth hormone may have a regulatory role in monocyte chemotaxis.

scholarly journals Differences in somatostatin receptor subtype expression in patients with acromegaly: new directions for targeted therapy?

HORMONES ◽  
2021 ◽  
Author(s):  
Lena Rass ◽  
Amir-Hossein Rahvar ◽  
Jakob Matschke ◽  
Wolfgang Saeger ◽  
Thomas Renné ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Monoclonal Antibodies ◽  
Tumor Size ◽  
Somatostatin Receptor ◽  
Human Growth ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Tissue Samples ◽  
Protein Levels ◽  
Histological Data

Abstract Purpose To analyze the expression of somatostatin receptor (SSTR)2a and 5 by immunohistochemistry (IHC) in surgically resected somatotrophic pituitary adenomas and to associate expression rates with tumor size and clinical, biochemical, and histological parameters and response to somatostatin analog (SA) therapy. Methods Forty-three microsurgically treated patients with histopathologically proven growth hormone (GH)–producing pituitary adenoma were included (WHO 2017). SSTR subtype expression was analyzed in adenoma tissues using monoclonal antibodies (Abcam, SSTR2a-UMB1, SSTR5-UMB4). Expression rates were classified as low (≤ 20% staining positivity), moderate (21–50%), and high (> 50%). Furthermore, biochemical parameters such as human growth hormone (hGH) and insulin-like growth factor-1 (IGF-1) levels were measured and clinical, biochemical, radiological, and histological data were evaluated. Results Of the 43 patients included in this study, 28 were female and 15 were male. The median age was 52 years (range 17–72 years). The median tumor size was 1.2 cm (range: 0.13–3.93 cm). All resected tumors showed positivity for somatotrophic hormone (STH). In all tissue samples, SSTR2a signal expression was detectable in immunohistochemistry, while only 39 samples were positive for SSTR5. Thirty-six samples had a high expression of SSTR2a, while three had a moderate and four a low SSTR2a signal. In comparison, SSTR5 signal was high in 26 out of 43 samples, while seven adenomas showed a moderate and six cases a low expression rate of SSTR5. The median IGF-1 was 714.2 µg/l and the median GH 19.6 mU/l (= 6.53 µg/l). The present study indicates that there is no significant relationship between the expression rates of receptor subtypes and the parameters we analyzed. However, our study revealed that smaller adenomas have a lower baseline GH level (p = 0.015), Conclusion IHC with monoclonal antibodies appears to be a suitable method to determine the expression rates of SSTR2a and 5 at protein levels, as it is not possible to draw conclusions regarding receptor subtypes solely on the basis of the parameters analyzed.

scholarly journals Distal Lung Microenvironment Triggers Release of Mediators Recognized as Potential Systemic Biomarkers for Idiopathic Pulmonary Fibrosis

2021 ◽  
Vol 22 (24) ◽  
pp. 13421
Author(s):  
Dimitrios Kalafatis ◽  
Anna Löfdahl ◽  
Per Näsman ◽  
Göran Dellgren ◽  
Åsa M. Wheelock ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Serum Proteins ◽  
Ex Vivo ◽  
Unmet Need ◽  
Response To Treatment ◽  
Serum Samples ◽  
Ex Vivo Model ◽  
Prognostic Assessment ◽  
New Biomarkers

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with an unmet need of biomarkers that can aid in the diagnostic and prognostic assessment of the disease and response to treatment. In this two-part explorative proteomic study, we demonstrate how proteins associated with tissue remodeling, inflammation and chemotaxis such as MMP7, CXCL13 and CCL19 are released in response to aberrant extracellular matrix (ECM) in IPF lung. We used a novel ex vivo model where decellularized lung tissue from IPF patients and healthy donors were repopulated with healthy fibroblasts to monitor locally released mediators. Results were validated in longitudinally collected serum samples from 38 IPF patients and from 77 healthy controls. We demonstrate how proteins elevated in the ex vivo model (e.g., MMP7), and other serum proteins found elevated in IPF patients such as HGF, VEGFA, MCP-3, IL-6 and TNFRSF12A, are associated with disease severity and progression and their response to antifibrotic treatment. Our study supports the model’s applicability in studying mechanisms involved in IPF and provides additional evidence for both established and potentially new biomarkers in IPF.

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