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Toward the Development of a Test for Growth Hormone (GH) Abuse: A Study of Extreme Physiological Ranges of GH-Dependent Markers in 813 Elite Athletes in the Postcompetition Setting

University of Naples Federico II, Napoli, Campania, Italy
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.31). 02/2005; 90(2):641-9. DOI: 10.1210/jc.2004-0386
Source: PubMed

ABSTRACT There is a need to develop a test to detect GH abuse by elite athletes. Measured levels of GH in blood or urine, however, provide little information on the GH-IGF-I axis. Previous studies have identified a series of indirect markers of GH action that are markedly altered by the administration of GH, but to a lesser degree by acute exercise. This study was undertaken to determine the physiological range of these GH-dependent variables in elite athletes after a competitive event to determine whether such values differ from resting values in normal and athletic subjects and to establish whether any adjustments to this range are required on the basis of age, gender, demographic characteristics, or the nature of the exercise performed. Serum samples were collected from 813 elite athletes (537 males and 276 females; age range, 17-64 yr) from 15 sporting disciplines within 2 h of completion of a major competitive event. IGF-I, IGF-binding protein 2 (IGFBP-2), IGFBP-3, acid-labile subunit, and the bone and soft tissue markers, osteocalcin, carboxyl-terminal propeptide of type I procollagen, carboxyl-terminal cross-linked telopeptide of type I collagen, and procollagen type III were measured. Sporting category, gender, age, height, weight, body mass index (BMI), and racial group of the athlete were documented, and results were compared both to normative data and to values obtained from elite athletes under resting conditions. Forty-one percent of IGF-I values in male athletes and 41% of values in female athletes were above the upper limits of 99% reference ranges derived from resting values in a normal population. Postcompetition levels of all variables except carboxyl-terminal propeptide of type I procollagen and carboxyl-terminal cross-linked telopeptide of type I collagen differed from resting values. There was a consistent age-dependent fall in measured levels of all variables (P < 0.0001) with the exception of IGFBP-2, which increased with age (P < 0.0001). BMI, but not height, exerted a small, but significant, influence on several variables. After adjustment for age, there were no significant differences in the levels of any of the measured variables between sporting categories. IGFBP-2 and IGFBP-3 were lower in 35 black athletes compared with those in 35 white athletes matched for age, gender, height, BMI, and sporting category. We have demonstrated that there are predictable age-dependent levels of GH-dependent markers in elite athletes that are consistent even at the extremes of physical exertion and that these are independent of sporting category. Normative data applicable to white athletes are provided. This provides important groundwork for the development of a test for GH abuse, although these values may be specific for the reagents and assays used.

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    • "In humans, osteocalcin has been reported to be inversely associated with fat mass and fasting plasma glucose (Kanazawa et al. 2009, 2010; Kindblom et al. 2009; Pittas et al. 2009), serum leptin (Guadalupe-Grau et al. 2009; Reinehr and Roth 2010) and insulin resistance (Fernandez- Real et al. 2009; Pittas et al. 2009; Reinehr and Roth 2010; Shea et al. 2009). Serum osteocalcin may be increased (Herrmann et al. 2007; Maimoun et al. 2006) reduced (Healy et al. 2005; Herrmann et al. 2007; Kerschan-Schindl et al. 2009; Malm et al. 1993; Mouzopoulos et al. 2007) or remain unchanged after high-intensity (Ehrnborg et al. 2003; Kristoffersson et al. 1995) or mild-intensity exercise (Wallace et al. 2000; Welsh et al. 1997). After prolonged exercise most studies report reduction in serum osteocalcin concentration (Kerschan-Schindl et al. 2009; Malm et al. 1993; Mouzopoulos et al. 2007). "
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    • "In humans, osteocalcin has been reported to be inversely associated with fat mass and fasting plasma glucose (Kanazawa et al. 2009, 2010; Kindblom et al. 2009; Pittas et al. 2009), serum leptin (Guadalupe-Grau et al. 2009; Reinehr and Roth 2010) and insulin resistance (Fernandez- Real et al. 2009; Pittas et al. 2009; Reinehr and Roth 2010; Shea et al. 2009). Serum osteocalcin may be increased (Herrmann et al. 2007; Maimoun et al. 2006) reduced (Healy et al. 2005; Herrmann et al. 2007; Kerschan-Schindl et al. 2009; Malm et al. 1993; Mouzopoulos et al. 2007) or remain unchanged after high-intensity (Ehrnborg et al. 2003; Kristoffersson et al. 1995) or mild-intensity exercise (Wallace et al. 2000; Welsh et al. 1997). After prolonged exercise most studies report reduction in serum osteocalcin concentration (Kerschan-Schindl et al. 2009; Malm et al. 1993; Mouzopoulos et al. 2007). "
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    ABSTRACT: Osteocalcin is a hormone produced by osteoblasts which acts as a negative regulator of fat mass, protecting against diet induced obesity and insulin resistance in rodents. To determine if an acute increase in osteocalcin concentration is associated with opposed changes in circulating leptin levels and insulin resistance we studied 15 middle and long distance male triathletes, (age 32.1 ± 6.9 years), before and 48 h after an Olympic (OT) or an Ironman (IT) triathlon competition. Muscle power, anaerobic capacity, body composition (dual-energy X-ray absorptiometry), and serum concentrations of testosterone, dihydrotestosterone, osteocalcin, leptin, glucose, insulin and insulin resistance (HOMA) were determined pre- and post-race. Pre- and 48 h post-race total and regional lean body mass was not altered, but fat mass was similarly increased (~250 g) 48 h after the competitions. This elicited an increase in plasma leptin of 33% after the IT while it remained unchanged after the OT, likely due to a 25% increase in plasma osteocalcin which occurred only after the OT (all p < 0.05). Post-race HOMA remained unchanged in OT and IT. Performance was normalized 48 h after the competitions, with the exception of a slightly lower jumping capacity after the IT. Serum testosterone concentration tended to decrease by 10% after the IT whilst dihydrotestosterone was reduced by 24% after the IT. In conclusion, an acute increase in serum osteocalcin concentration blunts the expected increase of serum leptin concentration that should occur with fat mass gain. This study provides evidence for osteocalcin as a negative regulator of serum leptin in humans.
    Arbeitsphysiologie 10/2010; 110(3):635-43. DOI:10.1007/s00421-010-1550-3 · 2.30 Impact Factor
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    • "In both the GH-2000 and 2004 studies, the double blind rhGH administration studies were undertaken in amateur athletes for ethical reasons. During the statistical analysis of the GH- 2000 study, it was found that IGF-I, P-III-P and GH-2000 score were significantly higher in professional athletes than amateur athletes [11]. Since the methodology will only be used in elite athletes, this required an adjustment of the cut-off point in the GH-2000 score to accommodate the higher baseline values seen in elite athletes [4]. "
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