title: Biochemical markers of recombinant human insulin-like growth factor-I (rhIGF-I)/rhIGF binding protein-3 (rhIGFBP-3) misuse in athletes.
abstract: Insulin-like growth factor-I (IGF-I) is reportedly misused by elite athletes, either alone or with growth hormone (GH). The GH-2000 and GH-2004 research groups previously developed a method for detecting GH misuse based on the GH-sensitive markers IGF-I and procollagen type III amino-terminal propeptide (P-III-NP). Both markers increase in response to rhIGF-I/rhIGF binding protein-3 (rhIGFBP-3) administration in recreational athletes. The aim of this pilot study was to assess the effect of rhIGF-I/rhIGFBP-3 administration on other serum markers of the GH-IGF axis and on other bone and collagen markers. Twenty-six female and 30 male recreational athletes were randomized to 28 days' treatment with placebo or rhIGF-I/rhIGFBP-3 complex, followed by 56 days' washout. GH-IGF axis markers (IGFBP-2, IGFBP-3, acid-labile subunit (ALS) and IGF-II) and bone and collagen markers (procollagen type I carboxy-terminal propeptide (PICP), type I collagen cross-linked carboxy-terminal telopeptide (ICTP) and osteocalcin) were measured using commercial immunoassays. In women in the high dose treatment group, mean IGF-II decreased by 53% (P=0.0028) on Day 21. Mean IGFBP-2 increased by 119% (P=0.0039) and mean ALS decreased by 40% (P=0.0022) on Day 21. There were no significant changes in IGFBP-3, osteocalcin, ICTP or PICP. In men in the high dose group, mean IGF-II decreased by 51% on Day 21 (P<0.0001). Mean IGFBP-2 increased by 125% on Day 21 (P=0.0003). There were no significant changes in IGFBP-3, ALS, osteocalcin, ICTP or PICP. Serum IGFBP-2 and IGF-II may be useful markers of rhIGF-I/rhIGFBP-3 administration in both women and men while ALS may also be a useful marker in women; these markers are now undergoing further evaluation.
authors.affiliation: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Nishan
authors.initials: N
authors.lastname: Guha
authors.forename: Ioulietta
authors.initials: I
authors.lastname: Erotokritou-Mulligan
authors.forename: Simon P
authors.initials: SP
authors.lastname: Nevitt
authors.forename: Michael
authors.initials: M
authors.lastname: Francis
authors.forename: Christiaan
authors.initials: C
authors.lastname: Bartlett
authors.forename: David A
authors.initials: DA
authors.lastname: Cowan
authors.forename: E Eryl
authors.initials: EE
authors.lastname: Bassett
authors.forename: Peter H
authors.initials: PH
authors.lastname: Sönksen
authors.forename: Richard I G
authors.initials: RI
authors.lastname: Holt
mesh_terms: D000293:Adolescent; D000328:Adult; D056352:Athletes; D015415:Biomarkers / Q000097:blood; D001842:Bone and Bones / Q000737:chemistry; D003094:Collagen / Q000032:analysis; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000008:administration & dosage / Q000032:analysis*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000032:analysis*; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000032:analysis; D015813:Substance Abuse Detection / Q000379:methods; D055815:Young Adult
chemical_list: D015415:Biomarkers; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D003094:Collagen
keywords: Growth Hormone; IGF-I; doping; markers; misuse