Novel serum protein biomarkers indicative of growth hormone doping in healthy human subjects

Ding, Juan; Okada, Shigeru; Jørgensen, Jens Otto Lunde; Kopchick, John J.

doi:10.1002/pmic.201100077

Cited by 14 publications

(11 citation statements)

References 32 publications

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“…The other proteins investigated, VDBP and decorin, did not change in their respective levels during or after the recGH administration, indicating that these proteins are not likely to be informative biomarkers of GH administration in athletes. It needs to be emphasized that in addition to the proteins studied here, some other putative GH biomarkers from omics studies warrant confirmation such as apolipoprotein L1, alpha‐HS‐glycoprotein, lumican, alpha‐1 antitrypsin, total plasma transthyretin, and hemoglobin β subunit 16,26 …”

Section: Discussionsupporting

confidence: 88%

Longitudinal studies of putative growth hormone (GH) biomarkers and hematological and steroidal parameters in relation to 2 weeks administration of human recombinant GH

Sieckmann

Elmongy

Ericsson

et al. 2020

Drug Testing and Analysis

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The detection of low doses of recombinant growth hormone is a challenge in antidoping testing. Future testing may lead toward the longitudinal monitoring of IGF‐I and P‐III‐NP in an endocrine module. Additional biomarkers, for example vitamin D binding protein, alpha‐HS‐glycoprotein, fibronectin 1, and decorin have been identified in different omics studies. This was a longitudinal study of the usefulness of these putative biomarkers in relation to 2 weeks administration of low doses of recombinant growth hormone in healthy male volunteers. Moreover, the hematological parameters included in the athlete biological passport were studied as well as the serum concentration of testosterone and dihydrotestosterone. Fibronectin 1 increased by 20% during the treatment period (P ˂ 0.05), confirming the previous finding. Alpha‐HS‐glycoprotein decreased by 25% up to 3 weeks after treatment (P ˂ 0.05), contradicting previous results. The addition of fibronectin 1 increased the likelihood of detecting recombinant growth hormone intake based on individual calculated thresholds in some of the participants compared with the GH2000, IGF‐I, and P‐III‐NP. The multiplication of fibronectin 1 concentration by IGF‐I resulted in the most profound (up to 4‐fold) changes. A minor 15% increase (P = 0.003) in the reticulocyte percentage was observed, but the changes did not lead to any atypical profile based on individual passport thresholds. Vitamin D binding protein, decorin, testosterone, and dihydrotestosterone were not affected by growth hormone. Dihydrotestosterone sulfate was negatively correlated with IGF‐I at baseline (R = –0.50, P = 0.003) and post dose (R = –0.59, P = 0.01). In conclusion, fibronectin 1 was verified as a promising future biomarker for detecting low doses of recombinant growth hormone.

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Section: Discussionsupporting

confidence: 88%

Longitudinal studies of putative growth hormone (GH) biomarkers and hematological and steroidal parameters in relation to 2 weeks administration of human recombinant GH

Sieckmann

Elmongy

Ericsson

et al. 2020

Drug Testing and Analysis

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“…We also identified apolipoprotein A-1, alpha-1 antitrypsin, and inter-alpha trypsin inhibitor heavy chain H4 proteins as differentially expressed in one of the analysis Phases only, so, were not evaluated further. Interestingly, previous studies have reported these three proteins to be differentially expressed in rGH or CJC-1295 (an analogue of growth hormone releasing hormone), administered subjects, so while they were not followed further by us, some concordance was observed 21 , 22 .…”

Section: Resultsmentioning

confidence: 80%

Plasma biomarker proteins for detection of human growth hormone administration in athletes

Tan

Lee

Pascovici

et al. 2017

Sci Rep

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Human growth hormone (GH) is a naturally occurring hormone secreted by the pituitary gland with anabolic and growth-promoting activities. Since an increased availability of recombinant GH (rGH) for the treatment of GH-deficient patients, GH has been abused in sports and it is prohibited. “GH-isoform” and “biomarkers” tests are currently available for detection of GH abuse in sports, however both methods suffer from shortcomings. Here, we report on a proteomic approach to search for novel protein biomarkers associated with rGH administration in non-elite athletes. In this study, participants received either placebo or rGH for 8 weeks, and were followed over a 6-week washout period. We used 2-D DIGE and iTRAQ LC-MS/MS analyses to expose rGH-dependent marker proteins. Eight rGH-dependent plasma proteins namely apolipoproptein-L1, alpha-HS-glycoprotein, vitamin D-binding protein, afamin, insulin-like growth factor-binding protein-3, insulin-like growth factor-binding protein-ALS, lumican and extracellular matrix proteins 1 were identified. Apolipoprotein L1 and alpha-HS-glycoprotein were validated by Western blots to confirm their identities and expression patterns in rGH- and placebo-treated subject cohorts. Independent confirmation of these putative GH-responsive biomarkers would be of value for clinical practices and may have sports anti-doping utility.

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“…2D Western blotting was used to validate the three isoforms, because a normal WB would not have allowed distinguishing between the different isoforms (all with very similar molecular weight), since the antibodies were not raised against one of the specific isoforms of the proteins. Therefore, the only way to distinguish between them was to separate the different isoforms by 2-DE prior to the immunochemical reaction [ 15 ]. Western blotting and 2D Western blotting protein expressions were significantly higher in the leiomyoma compared to the myometrium, confirming the results obtained from the 2-DE analysis ( Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

A Proteomic Approach for the Identification of Up-Regulated Proteins Involved in the Metabolic Process of the Leiomyoma

Ura

Scrimin

Arrigoni

et al. 2016

IJMS

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Uterine leiomyoma is the most common benign smooth muscle cell tumor of the uterus. Proteomics is a powerful tool for the analysis of complex mixtures of proteins. In our study, we focused on proteins that were upregulated in the leiomyoma compared to the myometrium. Paired samples of eight leiomyomas and adjacent myometrium were obtained and submitted to two-dimensional gel electrophoresis (2-DE) and mass spectrometry for protein identification and to Western blotting for 2-DE data validation. The comparison between the patterns revealed 24 significantly upregulated (p < 0.05) protein spots, 12 of which were found to be associated with the metabolic processes of the leiomyoma and not with the normal myometrium. The overexpression of seven proteins involved in the metabolic processes of the leiomyoma was further validated by Western blotting and 2D Western blotting. Four of these proteins have never been associated with the leiomyoma before. The 2-DE approach coupled with mass spectrometry, which is among the methods of choice for comparative proteomic studies, identified a number of proteins overexpressed in the leiomyoma and involved in several biological processes, including metabolic processes. A better understanding of the mechanism underlying the overexpression of these proteins may be important for therapeutic purposes.

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Novel serum protein biomarkers indicative of growth hormone doping in healthy human subjects

Cited by 14 publications

References 32 publications

Longitudinal studies of putative growth hormone (GH) biomarkers and hematological and steroidal parameters in relation to 2 weeks administration of human recombinant GH

Longitudinal studies of putative growth hormone (GH) biomarkers and hematological and steroidal parameters in relation to 2 weeks administration of human recombinant GH

Plasma biomarker proteins for detection of human growth hormone administration in athletes

A Proteomic Approach for the Identification of Up-Regulated Proteins Involved in the Metabolic Process of the Leiomyoma

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