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The Growth Hormone/Insulin-Like Growth Factor-I Axis Hormones and Bone Markers in Elite Athletes in Response to a Maximum Exercise Test

Endocrine Division, Department of Internal Medicine (C.E., B.-A.B., T.R.), Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden; Sports Medicine Research Unit, Bispebjerg Hospital (K.H.W.L.), DK-2400 Copenhagen NV, Denmark; Department of Medicine M (Endocrinology and Diabetes), Aarhus University Hospital (R.D., J.S.C.), DK-8000 Aarhus, Denmark; Department of Clinical Chemistry, Sahlgrenska University Hospital (P.-A.L.), S-413 45 Göteborg, Sweden; Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital (R.C.B.), St. Leonards 2065, New South Wales, Australia; Department of Endocrinology, St. Thomas’s Hospital (M.A.B., M.-L.H., C.P.), SE1 7EH London, United Kingdom; and Department of Clinical Medicine and Cardiovascular Sciences, University Federico II (S.L., R.N.), 80131 Naples, Italy

Address all correspondence and requests for reprints to: Christer Ehrnborg, Endocrine Division, Department of Internal Medicine, Gröna stråket 8, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. E-mail: christer.ehrnborg{at}medic.gu.se.

The aim of the GH-2000 project is to develop a method for detecting GH doping among athletes. Previous papers in the GH-2000 project have proposed that a forthcoming method to detect GH doping will need specific components from the GH/IGF-I axis and bone markers because these specific variables seem more sensitive to exogenous GH than to exercise. The present study examined the responses of the serum concentrations of these specific variables to a maximum exercise test in elite athletes from selected sports. A total of 117 elite athletes (84 males and 33 females; mean age, 25 yr; range, 18–53 yr) from Denmark, the United Kingdom, Italy, and Sweden participated in the study. The serum concentrations of total GH, GH22 kDa, IGF-I, IGF binding protein (IGFBP)-2, IGFBP-3, acid-labile subunit, procollagen type III (P-III-P), and the bone markers osteocalcin, carboxy-terminal cross-linked telopeptide of type I collagen (ICTP), and carboxy-terminal propeptide of type I procollagen were measured.

The maximum exercise test showed, in both genders, a peak concentration of total GH (P < 0.001) and GH22 kDa (P < 0.001) by the time exercise ended compared with baseline, and a subsequent decrease to baseline levels within 30–60 min after exercise. The mean time to peak value for total GH and GH22 kDa was significantly shorter in males than females (P < 0.001). The components of the IGF-I axis showed a similar pattern, with a peak value after exercise compared with baseline for IGF-I (P < 0.001, males and females); IGFBP-3 (P < 0.001, males and females); acid-labile subunit [P < 0.001, males; not significant (NS), females], and IGFBP-2 (P < 0.05, females; NS, males).

The serum concentrations of the bone markers ICTP (P < 0.001, males; P < 0.05, females) and P-III-P (P < 0.001, males and females) increased in both genders, with a peak value in the direct post-exercise phase and a subsequent decrease to baseline levels or below within 120 min.

The osteocalcin and propeptide of type I procollagen values did not change during the exercise test. Specific reference ranges for each variable in the GH/IGF-I axis and bone markers at specific time points are presented. Most of the variables correlated negatively with age.

In summary, the maximum exercise test showed a rather uniform pattern, with peak concentrations of the GH/IGF-I axis hormones and the bone markers ICTP and P-III-P immediately after exercise, followed by a subsequent decrease to baseline levels. The time to peak value for total GH and GH22 kDa was significantly shorter for females compared with males. This paper presents reference ranges for each marker in each gender at specific time points in connection to a maximum exercise test to be used in the development of a test for detection of GH abuse in sports.

This study was supported by grants from the European Union (BIOMED 2 Project Number BMH4 CT 950678) and the International Olympic Committee. Additional financial support and recombinant human GH were provided by Novo Nordisk and Pharmacia & Upjohn. The study was also supported with funds from the Göteborg Society of Medicine and the Swiss Foundation for Research. This study was part of the GH-2000 project, a research program performed within the competitive EU BioMed2 Research Programme, with additional support from the universities of Aarhus, Gothenburg, Naples, and London.

Abbreviations: ALS, Acid-labile subunit; bpm, beats per minute; CV, coefficient(s) of variation; HR, heart rate; ICTP, carboxy-terminal cross-linked telopeptide of type I collagen; IGFBP, IGF binding protein; NS, not significant; OC, oral contraceptive(s); PICP, carboxy-terminal propeptide of type I procollagen; P-III-P, procollagen type III; PV, plasma volume.

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