Influence of intravenous administration of growth hormone releasing peptide-2 (GHRP-2) on detection of growth hormone doping: growth hormone isoform profiles in Japanese male subjects.
Administration of exogenous 22 kDa recombinant human growth hormone (rhGH) suppresses the non-22 kDa pituitary growth hormone (GH) secretion by negative feedback; then, the elevated 22 kDa GH to non-22 kDa GH ratio (Rec/Pit ratio) can be utilized to detect doping with rhGH (isoform differential immunoassay). The influence of intravenous administration of growth hormone releasing peptide GHRP-2 on the isoform differential immunoassay for detecting rhGH doping has been investigated.In this study, a reference population (n=100) was used, with 0.04 mg/kg rhGH subcutaneous administration (n=5), 100 μg of GHRP-2 intravenous administration (n=10) and 0.04 mg/kg rhGH combined with 100 μg of GHRP-2 (n=10) in Japanese male subjects. The results indicated that the low dose (0.04 mg/kg) of rhGH led to significantly increased Rec/Pit ratio compared with the Japanese reference limit (P < 0.001). Because GHRP-2 dose led to increases in concentrations of both recombinant GH (recGH) and pituitary GH (pit GH), no significant change in the Rec/Pit ratio was observed (P > 0.05). In a combined administration study, after GHRP-2 dose the Rec/Pit ratios decreased to 39.9-43.9% compared with the elevated ratio caused by the rhGH dose.The results indicated that GHRP-2 administration cannot only be detected by the isoform differential immunoassay but also masks rhGH doping. The analysis of GHRP-2 was found to be suitable for compensating for the disadvantages of the isoform differential immunoassay because GHRP-2 and its metabolite (AA-3) in urine could be detected during the periods of masking of the Rec/Pit ratio by means of liquid chromatography/tandem mass spectrometry.
Anti-Doping Center, Mitsubishi Chemical Medience Corporation, 3-30-1 Shimura, Itabashi-ku, Tokyo, Japan. Okano.Masato@mk.medience.co.jp
Masato
M
Okano
Yasunori
Y
Nishitani
Mitsuhiko
M
Sato
Ayako
A
Ikekita
Shinji
S
Kageyama
D004300:Doping in Sports; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000032:analysis*; D006801:Humans; D007118:Immunoassay; D007275:Injections, Intravenous; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007564:Japan; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage* / Q000378:metabolism / Q000652:urine; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D020033:Protein Isoforms / Q000008:administration & dosage / Q000032:analysis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000032:analysis; D015813:Substance Abuse Detection / Q000379:methods
D009842:Oligopeptides; D010446:Peptide Fragments; D011347:Procollagen; D020033:Protein Isoforms; D011994:Recombinant Proteins; C041876:procollagen Type III-N-terminal peptide; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C091874:growth hormone-releasing peptide-2