Detection of doping with human growth hormone

Wu, Zida; Bidlingmaier, Martin; Dall, Rolf; Strasburger, Christian J.

doi:10.1016/s0140-6736(99)00775-8

Cited by 168 publications

(100 citation statements)

References 3 publications

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“…Intraassay coefficients of variation were 6.5 and 4.8% at concentrations of 0.8 and 6.2 mg/l respectively. Interassay coefficients of variation at the same concentrations were 8.2 and 6.1% respectively (12). Assay 2 was used for measuring the 20 kDa GH isoform using two monoclonal antibodies with no cross-reactivity to 22 kDa GH; intra-and interassay coefficients of variation were 5.4 and 7.5% at 1 mg/l and the limit of quantification was 0.05 mg/l (13).…”

Section: Hormone Measurementsmentioning

confidence: 99%

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Pharmacokinetics and pharmacodynamics of GH: dependence on route and dosage of administration

Keller¹,

Kratzsch

et al. 2007

eur j endocrinol

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Objective: Pharmacokinetic and pharmacodynamic data after recombinant human GH (rhGH) administration in adults are scarce, but necessary to optimize replacement therapy and to detect doping. We examined pharmacokinetics, pharmacodynamics, and 20 kDa GH after injection of rhGH at different doses and routes of administration. Design: Open-label crossover study with single boluses of rhGH. Methods: Healthy trained subjects (10 males, 10 females) received bolus injections of rhGH on three occasions: 0.033 mg/kg s.c., 0.083 mg/kg s.c., and 0.033 mg/kg i.m. Concentrations of 22 and 20 kDa GH, IGF-I, and IGF-binding proteins (IGFBP)-3 were measured repeatedly before and up to 36 h after injection. Results: Serum GH maximal concentration (C max ) and area under the time-concentration curve (AUC) were higher after i.m. than s.c. administration of 0.033 mg/kg (C max 35.5 and 12.0 mg/l; AUC 196.2 and 123.8). C max and AUC were higher in males than in females (P!0.01) and pharmacodynamic changes were more pronounced. IGFBP-3 concentrations showed no dose dependency. In response to rhGH administration, 20 kDa GH decreased in females and remained suppressed for 14-18 h (low dose) and 30 h (high dose). In males, 20 kDa GH was undetectable at baseline and throughout the study. Conclusions: After rhGH administration, pharmacokinetic parameters are mainly influenced by route of administration, whereas pharmacodynamic variables and 20 kDa GH concentrations are determined mainly by gender. These differences need to be considered for therapeutic use and for detection of rhGH doping.European Journal of Endocrinology 156 647-653

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Section: Hormone Measurementsmentioning

confidence: 99%

“…Unfortunately, rhGH has been misused, particularly in sport, and the methods to uncover such misuse have limitations (12,13). Exogenously administered rhGH is structurally identical to endogenous 22 kDa GH, which is the isoform predominantly secreted in humans (14,15).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of GH: dependence on route and dosage of administration

Keller¹,

Kratzsch

et al. 2007

eur j endocrinol

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“…Using assays based on a combination of relatively nonspecific polyclonal antibodies and specific assays using two monoclonal antibodies, each recognising specific epitopes on the 22 kDa and 20 kDa molecules, Strasburger and colleagues have developed a promising method of detecting rhGH abuse. They have shown that the absence of the 20 kDa isomer when 22 kDa GH is present in substantial amounts can be used as an indicator of exogenous rhGH administration and can thus form the basis of a test of GH abuse (Wu et al 1999). This is one way of tackling the detection of rhGH abuse but it will not, of course, detect administration of exogenous pituitary-derived GH.…”

Section: How Can We Detect Abuse With Gh?mentioning

confidence: 99%

Insulin, growth hormone and sport

Sönksen

2001

Journal of Endocrinology

169

145

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This review examines some interesting 'new' histories of insulin and reviews our current understanding of its physiological actions and synergy with GH in the regulation of metabolism and body composition. It reviews the history of GH abuse that antedates by many years the awareness of endocrinologists to its potent anabolic actions. Promising methods for detection of GH abuse have been developed but have yet to be sufficiently well validated to be ready for introduction into competitive sport. So far, there are two promising avenues for detecting GH abuse. The first uses immunoassays that can distinguish the isomers of pituitary-derived GH from the monomer of recombinant human GH. The second works through demonstrating circulating concentrations of one or more GH-sensitive substances that exceed the extremes of normal physiological variability. Both methods require blood rather than urine samples. The first method has a window of opportunity lasting about 24 h after an injection and is most suitable for 'out of competition' testing. The second method has reasonable sensitivity for as long as 2 weeks after the last injection of GH and is uninfluenced by extreme exercise and suitable for post-competition samples. This method has a greater sensitivity in men than in women. The specificity of both methods seems acceptably high but lawyers need to decide what level of scientific probability is needed to obtain a conviction. Both methods need further validation before implementation. Research work carried out as part of the fight against doping in sport has opened up a new and exciting area of endocrinology.

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“…Currently, Wu et al [13] demonstrated a method of checking GH doping using the ratio of 22K/total GH in serum. However, it is not possible to distinguish endogenous and exogenous GH after administration of GH.…”

Section: Discussionmentioning

confidence: 99%

Detection of Exogenous Growth Hormone (GH) Administration by Monitoring Ratio of 20kDa- and 22kDa-GH in Serum and Urine.

et al. 2000

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Abstract.We previously demonstrated that individual subjects have fairly constant ratios of serum concentrations of 20 kDa-(20K) and 22 kDa-GH (22K). The aim of this study is to demonstrate the possibility of utilizing the changes in the ratio of 20K/22K for detecting the exogenous administration of 22K. A male patient with idiopathic dilated cardiomyopathy (age 51) received 22K (4 U, s.c.) every other day. The concentrations of 20K and 22K in serum and urine were measured using enzyme-linked immunosorbent assays before and after administration.The administration of 22K increased total GH concentration, and markedly decreased the ratio of 20K/22K in serum, especially 2-10 h after the administration.From calculations, it became clear that the concentration of exogenous 22K reached a peak between 2-4 h after the administration and decreased to a negligible level after 24 h. The ratio of 20K/22K in the 0-24 h urine was 5 times lower than that in the 24-48 h urine. These data suggest that, by monitoring the ratio of 20K/22K in serum or urine, it is possible to determine whether or not GH has been externally administered and to calculate the serum GH that has been administered. GROWTH hormone (GH) therapy has been indicated for the treatment of GH deficient patients, and for some other indications and purposes [1, 2]. In addition, GH has been a subject to be tested for doping as one of prohibited drugs in sports [3, 4]. Two different kinds of GHs, 22 kDa-(22K) and 20 kDa-GH (20K), are known to be produced through alternative splicing of mRNA [5]. The 20K is a naturally occurring isoform lacking residues 32-46 of 22K [6] and comprises approximately 5-20% of circulating GH [7][8][9][10][11]. Recently, we have constructed two enzyme-linked immunosorbent assays (ELISAs), which specifically detect 20K or 22K in blood [9,10]. The level of circulating 20K was highly correlated to that of 22K in both normal subjects and patients, and the proportion of 20K in each individual subject was fairly constant even after pharmacological and physiological stimuli. Currently, we conducted a pharmacokinetic study of recombinant 20K in human subjects [11], and found that the 24-h profile of serum 20K level in the placebo group is parallel to that of 22K. In contrast, administration of 20K resulted not only in remarkable decrease in the ratio of serum concentrations of 20K and 22K, but also apparent suppression of GH secretion. These results strongly suggest that, by monitoring the ratio of 20K/22K either in serum or urine, it may be possible to determine whether or not GH has been externally administered and to calculate the concentration of serum GH that has been administered. The present

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Detection of doping with human growth hormone

Cited by 168 publications

References 3 publications

Pharmacokinetics and pharmacodynamics of GH: dependence on route and dosage of administration

Pharmacokinetics and pharmacodynamics of GH: dependence on route and dosage of administration

Insulin, growth hormone and sport

Detection of Exogenous Growth Hormone (GH) Administration by Monitoring Ratio of 20kDa- and 22kDa-GH in Serum and Urine.

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