Modification of the Metabolomic Profile Induced by Chronic Growth Hormone Administration in a Doping Model

Introduction Horses performance can be enhanced via growth hormone (GH) doping. The detection time for GH in blood is too short to allow detection during competition. GH not only affects the proteosynthesis in cells and tissues but can also cause long term metabolic variations. This study aimed to show the metabolomic modifications occurring after three months of GH treatment. Methods The study was performed on 20 Welsh ponies. 10 were injected with REPORCIN TM, an approved recombinant GH (30 mg.kg−1 per day) for 3 months and the other 10 comprised the control group. Blood samples were collected before GH treatment (T0), then 3 months later (T3). The NMR spectra acquired on the 40 serum samples were classified according to the factors (season, GH treatment) using the supervised multivariate orthogonal projection on latent structure (OPLS) method. A first OPLS model was computed with the control ponies (T0‐T3). The predictive component of this model was subtracted from the whole data (treated, controls at T0 and T3) to only retain the GH‐dependent variations. Results Before filtering seasonal effects, glucose, lipids and phospholipids were metabolites discriminating between T0 and T3 samples. After removing the seasonal effect, the OPLS model revealed the effect of GH treatment on protein metabolism through the modification of aromatic amino acids and branched chain amino acids. The variations of other metabolites (glycoproteins and lactate) were enhanced. Conclusions This study showed that chronic GH injection induced systemic metabolism modifications that can be detected using the NMR metabolomic method without neglecting the misleading effect of season. Ethical Animal Research Studies approved by “Comité regional d′éthique pour l′expérimentation animale Centre Limousin” Saisine N° CL2008_015. Sources of funding: French Agency against Doping (AFLD). Competing interests: none.