Detection of growth hormone abuse in sport

Powrie, Jake; Bassett, E. Eryl; Rosén, Thord; Jørgensen, Jens Otto Lunde; Napoli, Raffaele; Saccà, Luigi; Js, Christiansen; Bengtsson, Bengt‐Åke; Sönksen, Peter H.

doi:10.1016/j.ghir.2007.01.011

Cited by 136 publications

(148 citation statements)

References 19 publications

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“…The gender differences observed in the GH-2000 study were also seen in the current study (4)(5)(6). Although there were baseline differences in IGF1 and P-III-P between the GH-2000 and GH-2004 studies, there was no measurable difference in the peak IGF1 and P-III-P or maximal change in these markers following GH administration.…”

Section: Discussionsupporting

confidence: 73%

“…There was no significant correlation between IGF1 and P-III-P levels at baseline (PZ0.65). The GH-2000 scores are below zero in all groups reflecting the lower average IGF1 and P-III-P in amateur athletes compared with the elite athletes against whom the GH-2000 score was calibrated (4,11). This was also found in the original GH-2000 study (5,6).…”

Section: Baseline Characteristicsmentioning

confidence: 54%

“…The GH-2000 project proposed a test based on the measurement of the GH-sensitive markers, insulin-like growth factor 1 (IGF1) and type III pro-collagen (P-III-P) (4). Both of these markers rise in response to GH administration in a dose-dependent manner (5,6).…”

Section: Introductionmentioning

confidence: 99%

“…Although a single marker could be used, by combining markers in conjunction with gender-specific equations, 'discriminant functions', the sensitivity and specificity of the ability to detect GH abuse can be improved compared with single-marker analysis (4).…”

Section: Introductionmentioning

confidence: 99%

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The GH-2004 project: the response of IGF1 and type III pro-collagen to the administration of exogenous GH in non-Caucasian amateur athletes

Holt

Erotokritou‐Mulligan

McHugh

et al. 2010

European Journal of Endocrinology

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Context: The GH-2000 team proposed a method based on IGF1 and type III pro-collagen (P-III-P) to detect exogenously administered GH. As previous studies involved predominantly white European athletes, it is important to assess whether the response of these markers to recombinant human GH (rhGH) differs with ethnicity. Objective: To examine the response of serum IGF1 and P-III-P and GH-2000 score to rhGH in non-Caucasian amateur athletes. Design: Double-blind placebo-controlled rhGH administration study. Setting: Wellcome Trust Clinical Research Facility, Southampton General Hospital. Subjects: The study included 31 male and 14 female amateur athletes of different ethnicities. Intervention: The subjects were assigned to treatment with placebo or 0.1 IU/kg per day (low dose) or 0.2 IU/kg per day (high dose) rhGH for 28 days. Blood was collected weekly during treatment and on days 35, 42 and 84 during the washout period. Serum IGF1 and P-III-P were measured, and GH-2000 score was calculated. Results: IGF1, P-III-P and GH-2000 score rose in response to both low-and high-dose GH in both men and women. When compared with the Caucasian volunteers of the previous GH-2000 study, mean baseline and placebo-treated P-III-P and GH-2000 score were lower in GH-2004 men and women. Post-GH, however, peak IGF1 or P-III-P did not differ between studies but the peak GH-2000 score was lower in GH-2004 men. There was no difference between studies in the maximal change in IGF1, P-III-P and GH-2000 score in response to GH in either gender. Conclusions: These data do not support a significant ethnic effect on the peak or maximal response to rhGH.

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Section: Discussionsupporting

confidence: 73%

Section: Baseline Characteristicsmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The GH-2004 project: the response of IGF1 and type III pro-collagen to the administration of exogenous GH in non-Caucasian amateur athletes

Holt

Erotokritou‐Mulligan

McHugh

et al. 2010

European Journal of Endocrinology

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“…The GH-2000 project developed a detection methodology based on the measurement of two GH-dependent markers, Insulin-like Growth Factor-I (IGF-I) and type III procollagen (P-III-P), in conjunction with age and gender specific discriminant formulae. 4 The GH-2000 detection method provides high sensitivity and specificity 4 and has been validated in an independent GH administration study. 5 In addition, ethnicity 6 and sporting injuries 7 do not affect the reliability of the test.…”

Section: Introductionmentioning

confidence: 99%

The use of growth hormone (GH)‐dependent markers in the detection of GH abuse in sport: Physiological intra‐individual variation of IGF‐I, type 3 pro‐collagen (P‐III‐P) and the GH‐2000 detection score

Erotokritou‐Mulligan

Bassett

Cowan

et al. 2010

Clinical Endocrinology

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Summary Background Growth Hormone is abused by athletes for its lipolytic and anabolic properties. Its use is prohibited by the World Anti‐Doping Agency. The GH‐2000 project developed a methodology to detect its abuse using the concentrations of two GH‐dependent biomarkers, IGF‐I and type 3 procollagen (P‐III‐P). The sensitivity of this method may be improved by considering intra‐individual variability. Aim The aim of this study was to examine the intra‐individual variability of IGF‐I, P‐III‐P and the GH‐2000 score. Subjects and methods IGF‐I, P‐III‐P and GH‐2000 score were evaluated in four longitudinal studies involving 303 elite and 78 amateur athletes. Samples were collected over a period of up to 12 months from a total of 238 men and 143 women aged between 17 and 53 years (mean 24·2). Results The four studies showed good agreement with no apparent difference in within‐individual variation between amateur and elite athletes. The intra‐individual variability for IGF‐I ranged between 14–16% while the variability for P‐III‐P was 7–18%. No athlete tested positive for growth hormone during any of the studies. The overall mean intra‐individual variability of the GH‐2000 score was less than 0·6 units in all studies. Conclusions The high stability of marker levels suggests that concentrations are largely genetically determined. Adopting a test based on the concept of an athlete’s ‘passport’ or ‘profiling’ would take advantage of this and most likely increase the sensitivity of the test. These data also provide strong evidence that a positive test result for GH abuse would not occur as a result of chance variability.

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Detection of exogenous gene doping of IGF‐I by a real‐time quantitative PCR assay

Zhang

YongWei

et al. 2017

Biotech and App Biochem

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Gene doping can be easily concealed since its product is similar to endogenous protein, making its effective detection very challenging. In this study, we selected insulin-like growth factor I (IGF-I) exogenous gene for gene doping detection. First, the synthetic IGF-I gene was subcloned to recombinant adeno-associated virus (rAAV) plasmid to produce recombinant rAAV2/IGF-I-GFP vectors. Second, in an animal model, rAAV2/IGF-I-GFP vectors were injected into the thigh muscle tissue of mice, and then muscle and blood specimens were sampled at different time points for total DNA isolation. Finally, real-time quantitative PCR was employed to detect the exogenous gene doping of IGF-I. In view of the characteristics of endogenous IGF-I gene sequences, a TaqMan probe was designed at the junction of exons 2 and 3 of IGF-I gene to distinguish it from the exogenous IGF-I gene. In addition, an internal reference control plasmid and its probe were used in PCR to rule out false-positive results through comparison of their threshold cycle (Ct) values. Thus, an accurate exogenous IGF-I gene detection approach was developed in this study.

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Detection of growth hormone abuse in sport

Cited by 136 publications

References 19 publications

The GH-2004 project: the response of IGF1 and type III pro-collagen to the administration of exogenous GH in non-Caucasian amateur athletes

The GH-2004 project: the response of IGF1 and type III pro-collagen to the administration of exogenous GH in non-Caucasian amateur athletes

The use of growth hormone (GH)‐dependent markers in the detection of GH abuse in sport: Physiological intra‐individual variation of IGF‐I, type 3 pro‐collagen (P‐III‐P) and the GH‐2000 detection score

Detection of exogenous gene doping of IGF‐I by a real‐time quantitative PCR assay

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