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The University of Southampton
Growth Hormone 2004 Project

Background

Helen Glover and Heather Stanning

In 1991 the International Olympic Committee (IOC) realised that Growth Hormone (GH) was a new and increasingly misused powerful anabolic agent that was different from their previous experience with anabolic steroids. They invited Professor Peter Sönksen, a recognised expert on GH, to join the IOC Medical Commission and Sub-Commission ‘Doping and Biochemistry in Sport’. At this time the IOC anti-doping laboratories had little experience in protein analysis and the IOC itself had a negative attitude to research and it took until 1996 before they were persuaded to join and co-fund a multinational research group ‘GH-2000’, created within the European Union Biomed 2 Project (BMH4 CT95067) to develop a reliable methodology to detect misuse with growth hormone. Additional funding was provided by the two major European manufacturers of recombinant GH, Pharmacia and NovoNordisk and by the participating Universities in London and Canterbury (UK), Gothenburg (SE), Aarhus (DK) and Naples (IT).

In January 1999 'on time and within budget' the GH-2000 group proposed to the IOC a novel GH detection methodology based on measurement of insulin-like growth factor-I (IGF-I) and Procollagen Type III N-terminal pro-peptide (P-III-NP) in blood. This methodology could reliably detect GH abuse for up to 28 days since last injection of GH.

The IOC President Samaranch, pleased with the results of the project and keen to keep the team together, allocated another US$1 million to GH-2000 to finalise the research. Unfortunately as a consequence of internal conflict within the IOC, the Medical Commission chairman Prince Alexandre de Merode did not approve this grant and withdrew the funding before contracts were signed. He subsequently used this money to support the development of an alternative approach to detecting GH misuse, the isoform method.

The IOC now focussed on the isoform method and failed to capitalise on the GH-2000 results. As part of a reorganisation of doping-control the IOC passed the responsibility for ‘Dope Testing’ to a new authority, the newly formed ‘World Anti-Doping Agency (WADA)’.

Disappointed by the IOC’s withdrawal of funding Professor Sönksen sought funding from other sources while the project was in limbo. In December 2002 the United States Anti-Doping Agency (USADA) agreed funding for a research project led by Professors Richard Holt and Peter Sönksen from the University of Southampton to be known as GH-2004. This project addressed issues that arose concerning the validation of the GH-2000 method. WADA subsequently joined USADA with additional funding for the project; the aim was again to be able to identify “beyond reasonable doubt” GH dopers with minimal risk of false accusation. GH-2004 established co-operation with UK Sport and subsequently UK Anti-Doping (UKAD). Latterly the project has also received funding from the US Partnership for Clean Competition (PCC).

The Growth Hormone Detection Test

The methodology for detecting GH misuse developed by GH-2000 was based on the known actions of growth hormone in stimulating hepatic production of Insulin-like Growth Factor -I (IGF-I) and also elsewhere a collagen precursor N-terminal pro-peptide of type III collagen (P-III-NP). Under the influence of GH the serum concentrations of IGF-I and P-III-NP rise rapidly in a dose-dependent manner and remain elevated for some time after GH administration stops. Circulating blood levels of P-III-NP remain raised at least two weeks after stopping GH administration giving a potential ‘window of opportunity’ for the test of 14 days or more. The ‘sensitivity’ of the test depends on the dose and pattern of administration of growth hormone but in the GH-2000 and GH-2004 studies, the ‘sensitivity’ ranged from close to 100% of those taking GH to around 10% two weeks after the discontinuation of GH – a still useful value and potential deterrent (1).

References

(1) Powrie JK, Bassett EE, Rosen T, Jorgensen JO, Napoli R, Sacca L, Christiansen JS, Bengtsson BA, Sonksen PH. Detection of growth hormone abuse in sport. Growth Horm IGF Res 2007 June;17(3):220-6.

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