Abstract
Objective
Recombinant human growth hormone (rhGH) is used by some athletes and body builders with the aim of enhancing performance, building muscle and improving physique. Detection of the misuse of rhGH has proved difficult for a number of reasons. One of these is the effect of preceding exercise. In this randomised, double blind placebo-controlled study, we determined the effects of rhGH administration in male amateur athletes on two candidate markers of rhGH abuse, IGF-I and N-terminal pro-peptide of collagen type III (P-III-NP), following a bout of weightlifting exercise.
Design
Sixteen men entered a four-week general weight training programme to homogenise their activity profile. They then undertook repeated bouts of standardised leg press weightlifting exercise (AHRET-acute heavy resistance exercise test). Blood samples were taken before and up to one hour after the AHRET. After the first laboratory visit (Test 1), the subjects were randomly assigned to receive daily injections of either rhGH (0.1 IU kg− 1 day− 1) or placebo for two weeks. The AHRET was repeated after the two-week dosing period (Test 2) and a further test was undertaken following a one-week washout (Test 3).
Results
There was no effect of exercise on either IGF-I or P-III-NP in any test. Both markers were markedly elevated at Test 2 (p < 0.001), with P-III-NP remaining elevated at Test 3 in the GH administration group (p < 0.05). Application of the GH-2000 discriminant function positively identified GH administration in 17 of 40 blood samples taken at Test 2 from the rhGH group and none from the placebo group.
Conclusion
The data show that rhGH results in elevated levels of IGF-I and P-III-NP in well-trained individuals and that leg press weightlifting exercise does not affect these markers. The GH-2000 discriminant function identified four of eight subjects taking rhGH with no false positive results.
Introduction
Growth Hormone (GH) is a 191 amino acid peptide hormone secreted by the somatrotroph cells of the anterior pituitary with several important functions. Although long-term use of GH may be detrimental given the anomalies seen in patients with acromegaly [1], there is alleged widespread use of recombinant human (rh) GH among athletes [2] as well as reports of abuse in the wider community [3]. Recent studies show that rhGH may have particularly beneficial effects when used in combination with androgenic steroids on sprint capacity [4] and endurance [5], [6]. There is, however, very little other evidence of a performance-enhancing effect of rhGH in athletes or healthy individuals following rhGH administration [7], [8], [9] although there is a clear increase in fat-free mass [10]. GH may also have protein-sparing effects in catabolic situations [11], [12], [13].
The use of both rhGH and exogenous, pituitary derived GH is prohibited by the World Anti-Doping Agency and other major sporting bodies. Its detection is a challenge because endogenously produced GH is secreted in a pulsatile manner with naturally occurring peaks that often overlap with levels detected shortly after rhGH injection [8]. Furthermore, exercise is a known stimulator of GH secretion producing a response that is dependent upon the duration, type and intensity of exercise [14]. Further challenges for the detection of misuse relate to the fact that rhGH is identical in sequence to the most abundant GH isoform (22 kDa) found in the circulation. A test based on the relative proportions of 22 kDa and non-22 kDa GH isoforms in blood has been in use since the Athens Olympic Games in 2004 [15]. The principle of this is based on the premise that rhGH is exclusively 22 kDa and its administration down-regulates endogenous production of all GH isoforms, thus resulting in a shift in the ratio of GH isoforms. The limitation of this detection method is that the test is only effective within 12–24 h or so of the last injection and it is therefore likely to be most useful in unannounced out-of-competition testing. Such application, for example, resulted in English rugby league player Terry Newton being caught and accepting a two-year ban in 2010 [16].
An alternative test was proposed by the GH-2000 team based on the measurement of markers of rhGH administration rather than GH itself. Exogenous rhGH administration acutely increases circulating IGF-I [17], [18], [19] and IGF-I levels serve as a marker of altered GH function in pathological situations [20]. GH also affects markers of bone and collagen turnover such as N-terminal pro-peptide of collagen type III (P-III-NP) [21]. When combined with gender-specific and age-corrected discriminant function analysis, the use of IGF-I and P-III-NP is able to provide a sensitive and specific test to identify those taking rhGH [22]. The test has been validated using independent data sets from controlled studies and samples from athletes in after-competition settings [23], [24] and was introduced at the London Olympic Games subsequently leading to the disqualification of two Russian powerlifters at the Paralympic Games.
There were three aims of the present study. The first was to determine the effects of a two-week period of rhGH administration on circulating IGF-I and P-III-NP in a group of non-elite, but well-trained athletic men. The second was to determine the effects of an acute bout of high-resistance exercise on these markers following rhGH administration. The third was to determine whether the rhGH subjects could be distinguished from a control group by applying the GH-2000 discriminant function described by Powrie and coworkers [22].
Access through your organization
Check access to the full text by signing in through your organization.Access through your organization
Section snippets
Subjects
Sixteen men aged between 18 and 40 years (mean ± SD, age 22.5 ± 2.3 years, body mass 93.6 ± 5.9 kg), with a high level of physical training including regular high-resistance strength training and no illnesses or medications known to impair exercise or alter endocrine function, were recruited. A full physical examination was performed prior to trial entry. Subjects were weighed and their one-repetition maximum (1-RM) on a leg press (Technogym, Berkshire, UK) was determined (Table 1).
Study design
The study was a
Subject characteristics and adherence
Sixteen men enrolled in the study. One subject withdrew after the first test day but before the active arm of the study for personal reasons not connected with the study. The study was continued on the remaining 15 subjects. There were no statistically significant differences in age, body mass, or 1-RM between those randomised to GH or placebo groups at baseline (Table 1).
Adherence to the protocol, as assessed by counting the vials returned by the subjects, was 100%. In the group taking GH, the
Discussion
To our knowledge this is the first study to assess the effects of rhGH administration on P-III-NP and IGF-I in individuals who are undergoing strength exercise training. The main findings of this study are: 1) GH administration results in significant increases in both markers of rhGH administration, circulating IGF-I and P-III-NP; 2) the IGF-I response is undetectable after one week of wash out, but P-III-NP levels remain significantly elevated; 3) an acute bout of resistance exercise does not
Conclusion
The results presented herein show that administration of rhGH for two weeks to physically active, strength trained individuals resulted in significantly elevated levels of IGF-I and P-III-NP both before and after a bout of intense high-resistance strength training exercise. Exercise itself had no effect on these markers. In contrast to IGF-I, P-III-NP levels remain elevated for at least one week after cessation of administration. When applied to these data, the GH-2000 discriminant function
Acknowledgements
This study was funded by the World Anti-Doping Agency. rhGH was a gift from Novo Nordisk and the leg press machine was provided by Technogym. We acknowledge the work of the GH-2000 team and the other members of the GH-2004 team.
Cited by (6)
Functional training with blood occlusion influences muscle quality indices in older adults
2020, Archives of Gerontology and Geriatrics
Due to limited number of studies on training and P3NP, the effect of training on P3NP levels were less conclusive. For example, Velloso et al. (2013) reported no significant changes in serum P3NP in response to a bout of leg press exercise whilst Fragala, Jajtner et al. (2014) reported a non-significant increase in P3NP in response to a 6-week resistance training program. Similar to multifactorial phenomena, it is difficult to identify the exact mechanisms responsible for these discrepancies. View full text
Copyright © 2013 Elsevier Ltd. All rights reserved.