Genetic and protein biomarkers in blood for the improved detection of GH abuse

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 128; pp. 111 - 118
• Main Authors: Ferro, P., Ventura, R., Pérez-Mañá, C., Farré, M., Segura, J.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 05.09.2016; Elsevier
• Subjects: Adult; Biological Assay - methods; Biomarkers - blood; Dopatge en els esports; Doping abuse; Doping in Sports - methods; Doping substances; Female; Fibronectin; FN1; Growth hormone; Human Growth Hormone - blood; Humans; Insulin-Like Growth Factor I - metabolism; Male; Marcadors bioquímics; Proteomics - methods; RAB31; Recombinant Proteins - blood; Sports; Substance Abuse Detection - methods; Young Adult; FN1; RAB31; Growth hormone; Doping abuse; Fibronectin; Doping substances
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2016.05.022

Increase of FN1 and RAB31 expression in PBL and FN1 concentrations in serum samples after treatment with recombinant growth hormone. [Display omitted] •Expression of FN1 and RAB31 genes in lymphocytes appear as sensitive markers of rhGH administration.•FN1 protein in serum also appears as a sensitive marker already 24h after the first rhGH dose.•FN1 gene and protein levels in serum are not influenced by gender, age, sport and other doping substances.•Serum and/or plasma can be used for FN1 concentrations measurements. Human Growth Hormone (hGH, somatotropin) is one of the relevant forbidden substances to be detected in sport drug testing. Since the appearance of recombinant hGH (rhGH) in the 80’s, its expansion and availability through the black market have increased, so the detection of its abuse continues to be a challenge at present. New techniques or biomarkers that are robust, reliable, sensitive and allowing a large detection time window are welcome. rhGH produces an increase of insulin-like growth factor 1 (IGF-1). FN1 (fibronectin 1) and RAB31 (member of RAS oncogene family) genes have been suggested as two potential biomarkers for IGF-1 abuse. Following this line, in the present study some genetic and proteomic approaches have been performed with fourteen healthy male subjects treated with rhGH (which produces increase of IGF-1 concentrations) to study FN1 gene, FN1 protein, RAB31 gene and RAB31 protein as potential biomarkers for rhGH abuse. The results showed that both, RAB31 and FN1 genes and FN1 protein could be potential biomarkers for rhGH administration. Preliminary assessments of gender, age, acute sport activities and GHRP-2 (pralmorelin, a rhGH releasing peptide) influence suggest they are not relevant confounding factors. Thus, the selected markers present high sensitivity and a larger detection window for rhGH detection than IGF-1 itself.