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Longitudinal studies of putative growth hormone (GH) biomarkers and hematological and steroidal parameters in relation to 2 weeks administration of human recombinant GH
Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.ORCID iD: 0000-0002-2485-4276
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Detection of low doses of recombinant growth hormone is a challenge in anti-doping testing. Future testing leads toward 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 decoin have been identified in different omics studies. Here we have longitudinally studied the usefulness of these putative biomarkers in relation to two weeks administration of low doses of recombinant growth hormone in healthy male volunteers. Moreover, we studied the hematological parameters included in the athlete biological passport as well as serum concentration of dihydrotestosterone-sulfate. Alpha-HS-glycoprotein decreased 25 % up to three weeks after treatment period (p˂0.05), whereas fibronectin increased 20 % during the treatment (p˂0.05). The addition of these two biomarkers increased the likelihood to detect recombinant growth hormone intake based on individual calculated thresholds in some of the participants as compared to the GH2000 score. A minor 10 % increase (p=0.003) in reticulocytes percentage and OFF-score was observed, but the changes did not lead to any atypical profile based on individual passport thresholds. Vitamin D binding protein, decoin and dihydrotestosterone-sulfate were not affected by recombinant growth hormone. Dihydrotestosterone-sulfate was negatively correlated with the IGF-I biomarker at baseline (R=-0.50, p=0.003) and post dose (R=-0.59, p=0.01). In conclusion we have verified Alpha-HS-glycoprotein and fibronectin 1 as promising future biomarkers for detecting low doses of recombinant growth hormone and further studies of these proteins are encouraged.

Keywords [en]
doping, growth hormone, IGF-I, fibronectin 1, alpha-HS-glycoprotein, DHT, athlete biological passport
National Category
Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
URN: urn:nbn:se:su:diva-172565OAI: oai:DiVA.org:su-172565DiVA, id: diva2:1348246
Available from: 2019-09-03 Created: 2019-09-03 Last updated: 2019-09-04Bibliographically approved
In thesis
1. Analytical Methods For Sports Drugs: Challenges and Approaches
Open this publication in new window or tab >>Analytical Methods For Sports Drugs: Challenges and Approaches
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Drugs used to enhance human performance in sport competitions are prohibited by the world anti-doping association (WADA). Biological samples from athletes are continuously tested for adverse analytical findings regarding the identity and/or quantity of the banned substances. The current thesis deals with the development of new analytical methods to determine the concentrations of certain drugs used by athletes and even by regular users for therapeutic purposes. The developed methods aim to analyze the contents of these drugs in the biological matrices; plasma, serum and saliva to provide a successful approach towards either doping detection or therapeutic monitoring. β-adrenergic blockers such as propranolol and metoprolol are used in sports to relief stress and as therapeutic agents in the treatment of hypertension. Both drugs are in chiral forms and available only as racemic mixtures. The different pharmacology of each enantiomer necessitates the monitoring of each enantiomer by stereoselective analytical technique such as chiral liquid chromatography for separation and mass spectrometry for selective detection. The Endogenous anabolic androgenic steroids (EAAS) on the other hand are only notoriously used in sports to increase muscle mass and strength. A method utilizing high-resolution mass spectrometry (HRMS) coupled to ultra-high performance liquid chromatography (UHPLC) was developed for the simultaneous determination of EAAS and their conjugated metabolites to provide a better insight into the steroidal module of the athlete biological passport (ABP). Moreover, the steroidal profile was assessed in serum using the proposed method after the administration of Growth hormone injection as an approach toward the implementation of a new endocrinological module based on steroids biomarkers to hormone doping.  Biological samples contain many components that may interfere with the analytical measurements. Therefore, sample preparation methods were developed using solid phase extraction (SPE) and miniaturized techniques such as microextraction by packed sorbents (MEPS) for the purification and pre-concentration of analytes prior to LC/MS analysis.

Place, publisher, year, edition, pages
Stockholm: Department of Environmental Science and Analytical Chemistry, Stockholm University, 2019. p. 89
Keywords
Sports Drugs, Doping in Sports, Steroids, LC-MS/MS, Chiral analysis, high-resolution mass spectrometry, Sample preparation, Biological samples, solid phase extraction
National Category
Analytical Chemistry
Research subject
Analytical Chemistry
Identifiers
urn:nbn:se:su:diva-172566 (URN)978-91-7797-835-0 (ISBN)978-91-7797-836-7 (ISBN)
Public defence
2019-10-18, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.

Available from: 2019-09-25 Created: 2019-09-03 Last updated: 2019-09-13Bibliographically approved

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