The GH-2004 project: the response of IGF1 and type III pro-collagen to the administration of exogenous GH in non-Caucasian amateur athletes

Abstract

Context: The GH-2000 team proposed a method based on IGF1 and type III pro-collagen (P-III-P) to detect exogenously administered GH. As previous studies involved predominantly white European athletes, it is important to assess whether the response of these markers to recombinant human GH (rhGH) differs with ethnicity. Objective: To examine the response of serum IGF1 and P-III-P and GH-2000 score to rhGH in non-Caucasian amateur athletes. Design: Double-blind placebo-controlled rhGH administration study. Setting: Wellcome Trust Clinical Research Facility, Southampton General Hospital. Subjects: The study included 31 male and 14 female amateur athletes of different ethnicities. Intervention: The subjects were assigned to treatment with placebo or 0.1 IU/kg per day (low dose) or 0.2 IU/kg per day (high dose) rhGH for 28 days. Blood was collected weekly during treatment and on days 35, 42 and 84 during the washout period. Serum IGF1 and P-III-P were measured, and GH-2000 score was calculated. Results: IGF1, P-III-P and GH-2000 score rose in response to both low-and high-dose GH in both men and women. When compared with the Caucasian volunteers of the previous GH-2000 study, mean baseline and placebo-treated P-III-P and GH-2000 score were lower in GH-2004 men and women. Post-GH, however, peak IGF1 or P-III-P did not differ between studies but the peak GH-2000 score was lower in GH-2004 men. There was no difference between studies in the maximal change in IGF1, P-III-P and GH-2000 score in response to GH in either gender. Conclusions: These data do not support a significant ethnic effect on the peak or maximal response to rhGH.

Short-term rhGH increases PIIINP, a biomarker of endothelial dysfunction

“…This equates to an average GH secretion of circa 0.67 mg and 0.83 mg in males and females respectively, per 24 hours [31]. The effect of rhGH in elevating PIIINP and IGF-I, corroborated similar research of short-term (four and two weeks) rhGH administration [16,17]. PIIINP concentration is currently considered an independent predictor of left ventricular end-diastolic pressure (LVEDP) and correlates with cardiac mortality and revascularization, providing an additional means of evaluating and managing patients with acute coronary syndrome [6].…”

“…IGF-I is believed to have a vascular protective role because it stimulates NO production from endothelial and vascular smooth muscle cells. The time frame and concentration levels of serum GH and IGF-I, from commencement of excess production, in acromegaly, to pathological symptomatology is still unknown .day -1 [38,16]) for four times longer (one month) than dosages used in the present study (0.019 mg.kg -1 .day -1 ). However, the researchers were attempting to identify a test for doping rather than assess CVD risk factors.…”

“…RhGH improves vascular ED in patients with chronic heart failure who are not deficient in endogenous growth hormone [15]. Short-term rhGH, four weeks (0.1 and 0.2 IU.kg -1 .day -1 ) and two weeks (0.1 IU.kg -1 .day -1 ) respectively, has been shown to significantly elevate PIIINP in healthy individuals by almost three times baseline levels [16,17]. The purpose of this original study was to examine the effects of one week's supraphysiological rhGH administration on PIIINP and specific CVD parameters in an apparently healthy group of strength training males.…”

Interlaboratory Agreement of Insulin-like Growth Factor 1 Concentrations Measured by Mass Spectrometry

“…Because each immunoassay platform has different reference ranges for IGF-1, it is difficult to provide specific guidelines for GH disease management. For antidoping applications, serum concentrations of IGF-1 and the N-terminal propeptide of type III procollagen are used in combination to detect GH abuse (5)(6)(7)(8)(9). This use of these 2 biomarkers was recently implemented in the 2012 Olympic Games in London and will soon be adopted in all 33 World Anti-Doping Agency (WADA)-accredited laboratories worldwide.…”

The development of decision limits for the implementation of the GH-2000 detection methodology using current commercial insulin-like growth factor-I and amino-terminal pro-peptide of type III collagen assays

“…These scores have not been standardised to have mean 0 and SD 1 (as in the previous GH-2000 [1] and GH-2004 publications [9][10][11][12][13]), and therefore the original proposed decision limit of 3.72 is no longer relevant.…”