Download PDF
Int J Sports Med 2006; 27(12): 976-983
DOI: 10.1055/s-2006-923864
Physiology & Biochemistry

© Georg Thieme Verlag KG Stuttgart · New York

Effect of Physical Fitness and Endurance Exercise on Indirect Biomarkers of Recombinant Growth Hormone Misuse: Insulin-Like Growth Factor I and Procollagen Type III Peptide

R. Abellan1 , 2 , R. Ventura1 , 2 , S. Pichini3 , R. Di Giovannandrea3 , M. Bellver4 , R. Olive4 , R. Pacifici3 , J. A. Pascual1 , 2 , P. Zuccaro3 , J. Segura1 , 2
  • 1Pharmacology Research Unit, Institut Municipal d'Investigació Mèdica, Barcelona, Spain
  • 2Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
  • 3Drug Research and Evaluation Department, Istituto Superiore di Sanitá, Roma, Italy
  • 4Centre d'Alt Rendiment, Sant Cugat, Barcelona, Spain
Further Information

Publication History

Accepted after revision: December 5, 2005

Publication Date:
11 April 2006 (online)

Also available at
    Permissions and Reprints

Abstract

Serum insulin-like growth factor-I (IGF‐I) and procollagen type III peptide (P‐III‐P) have been proposed as indirect biomarkers of rhGH misuse in sports. The purpose of the present study was to investigate concentrations of these biomarkers in athletes at different levels of physical fitness and endurance exercise. Serum total IGF‐I and P‐III‐P were measured in 96 elite athletes of various sports along the training season; in 21 recreational athletes at baseline non-exercising conditions and in another 129 recreational athletes before and after long-distance races (10 and 21 km). No differences were evidenced for IGF‐I concentrations, but statistically higher values of serum P‐III‐P were found in elite athletes compared to recreational ones. Among elite athletes, the specific sport did not affect serum IGF‐I. However, P‐III‐P was statistically higher in the sport performed by the youngest athletes (rhythmic gymnastics), even after correction of the logarithm of the concentration by the reciprocal of age. Over the training season, the within-athlete variabilities of IGF‐I and P‐III‐P in elite athletes were low (22.8 % and 21.7 %, respectively). Recreational athletes taking part in a 21 km competition race showed a significant increase in serum values of IGF‐I and P‐III‐P immediately after the event. Exercise workload and age had a significant effect on serum concentration of P‐III‐P, while age alone affected IGF‐I serum concentrations. Therefore, athlete's reference concentration ranges for doping detection should include subjects from as many different ages and sports as possible.

Key words

IGF‐I - P‐III‐P - athletes - GH doping detection - training

References

  • 1 Abellan R, Ventura R, Pichini S, Pascual J A, Pacifici R, Di Carlo S, Bacosi A, Segura J, Zuccaro P. Evaluation of immunoassays for the measurement of insulin-like growth factor-I and procollagen type III peptide, indirect biomarkers of recombinant human growth hormone misuse in sport.  Clin Chem Lab Med. 2005;  43 75-85
    CrossrefPubMedGoogle Scholar
  • 2 Borst S E, De Hoyos D V, Garzarella L, Vincent K, Pollock B H, Lowenthal D T, Pollock M L. Effects of resistance training on insulin-like factor-I and IGF binding proteins.  Med Sci Sports Exerc. 2001;  33 648-653
    PubMedGoogle Scholar
  • 3 Cappon J, Brasel J A, Mohan S, Cooper D M. Effect of brief exercise on circulating insulin-like growth factor.  J Appl Physiol. 1994;  76 2490-2496
    PubMedGoogle Scholar
  • 4 Dall R, Lange K HW, Kjaer M, Jorgensen J OL, Christiansen J S, Orskov H, Flyvbjerg A. No evidence of insulin-like growth factor-binding protein 3 proteolysis during a maximal exercise test in elite athletes.  J Clin Endocrinol Metab. 2001;  86 669-674
    CrossrefPubMedGoogle Scholar
  • 5 De Palo E F, Gatti R, Lancerin F, Cappelin E, Spinella P. Correlations of growth hormone (GH) and insulin-like growth factor I (IGF‐I): effects of exercise and abuse by athletes.  Clin Chim Acta. 2001;  305 1-17
    CrossrefPubMedGoogle Scholar
  • 6 Ehrnborg C, Lange K HW, Dall R, Christiansen J S, Lundberg P-A, Baxter R C, Boroujerdi M A, Bengtsson B-A, Healy M-L, Pentecost C, Longobardi S, Napoli R, Rosen T. The growth hormone/insulin-like growth factor-I axis hormones and bone markers in elite athletes in response to a maximum exercise test.  J Clin Endocrinol Metab. 2003;  88 394-401
    CrossrefPubMedGoogle Scholar
  • 7 Fleischmajer R, Perlish J S, Burgeson R E, Shaikh-Bahai F, Timpl R. Type I and type III collagen interactions during fibrillogenesis.  Ann NY Acad Sci. 1990;  580 161-175
    PubMedGoogle Scholar
  • 8 Ghigo E, Aimaretti G, Maccario M, Fanciulli G, Arvat E, Minuto F, Giordano G, Delitala G, Camanni F. Dose-response study of GH effects on circulating IGF‐I and IGFBP‐3 levels in healthy young men and women.  Am J Physiol. 1999;  39 E1009-E1013
    PubMedGoogle Scholar
  • 9 Healy M-L, Dall R, Gibney J, Basset E, Ehrnborg C, Pentecost C, Rosen T, Cittadini A, Baxter R C, Sonksen P H. Towards the development of a test for growth hormone abuse. Study of extreme physiological ranges of growth hormone dependent markers in 813 elite athletes in the post-competition setting.  J Clin Endocrinol Metab. 2005;  90 641-649
    PubMedGoogle Scholar
  • 10 Jahreis G, Hesse V, Schmidt H E, Scheibe J. Effect of endurance exercise on somatomedin-C/insulin-like growth factor I concentration in male and female runners.  Exp Clin Endocrinol. 1989;  94 89-96
    PubMedGoogle Scholar
  • 11 Jenkins P J. Growth hormone and exercise: physiology, use and abuse.  GH IGF Res. 2001;  Suppl A S71-S77
    PubMedGoogle Scholar
  • 12 Juul A, Bang P, Hertel N T, Main K, Dalgaard P, Jorgensen K, Muller J, Hall K, Skakkebaek N E. Serum insulin-like growth factor in 1030 healthy children, adolescents, and adults: Relation to age, sex, stage of puberty, testicular size, and body mass index.  J Clin Endocrinol Metab. 1994;  78 744-752
    CrossrefPubMedGoogle Scholar
  • 13 Kargotich S, Goodman C, Keast D, Morton D. The influence of exercise-induced plasma volume changes on the interpretation of biochemical parameters used for monitoring exercise, training and sport.  Sports Med. 1998;  26 101-117
    CrossrefPubMedGoogle Scholar
  • 14 Kicman A T, Miell J P, Teale J D, Powrie J, Wood P J, Laidler P, Milligan P J, Cowan D A. Serum IGF‐I and IGF binding proteins 2 and 3 as potential markers of doping with human GH.  Clin Endocrinol. 1997;  47 43-50
    CrossrefPubMedGoogle Scholar
  • 15 Koistinen H, Koistinen R, Selenius L, Ylikorkala O, Seppala M. Effect of marathon run on serum IGF‐I and IGF-bindings protein 1 and 3 levels.  J Appl Physiol. 1996;  80 760-764
    PubMedGoogle Scholar
  • 16 Koziris L P, Hickson R C, Chatterton R T, Groseth R T, Christie J M, Goldflies D G, Unterman T G. Serum levels of total and free IGF‐I and IGFBP‐3 are increased and maintained in long-term training.  J Appl Physiol. 1999;  86 1436-1442
    PubMedGoogle Scholar
  • 17 Longobardi S, Keay N, Ehrnborg C, Cittadini A, Rosen T, Dall R, Boroujerdi M A, Bassett E E, Healy M L, Pentecost C, Wallace J D, Powrie J, Jorgensen J O, Sacca L. Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sports: a double blind, placebo-controlled study. The GH-2000 Study Group.  J Clin Endocrinol Metab. 2000;  85 1505-1512
    CrossrefPubMedGoogle Scholar
  • 18 Marx J O, Ratamess N A, Nindl B C, Gotshalk L A, Volek J S, Dohi K, Bush J A, Gomez A L, Mazzetti S A, Fleck S J, Häkkinen K, Newton R U, Kraemer J. Low-volume circuit versus high-volume periodized resistance training in women.  Med Sci Sports Exerc. 2001;  33 635-643
    CrossrefPubMedGoogle Scholar
  • 19 Nguyen U N, Mougin F, Simon-Rigaud M L, Rouillon J D, Marguet P, Regnard J. Influence of exercise duration on serum insulin-like growth factor and its binding proteins.  Eur J Appl Physiol. 1998;  78 533-537
    CrossrefPubMedGoogle Scholar
  • 20 Nindl B C, Kraemer W J, Marx J O, Arciero P J, Dohi K, Kellogg M D, Loomis G A. Overnight responses of the circulating IGF‐I system after acute, heavy-resistance exercise.  J Appl Physiol. 2001;  90 1319-1326
    PubMedGoogle Scholar
  • 21 Nindl B C, Castellani J W, Young A J, Patton J F, Khosravi M J, Diamandi A, Montain S J. Differential responses of IGF‐I molecular complexes to military operational field training.  J Appl Physiol. 2003;  95 1083-1089
    PubMedGoogle Scholar
  • 22 Quarmby V, Quan C, Ling V, Compton P, Canova-Davis E. How much insulin-like growth factor I (IGF‐I) circulates? Impact of standardization on IGF‐I assay accuracy.  J Clin Endocrinol Metab. 1998;  83 1211-1216
    CrossrefPubMedGoogle Scholar
  • 23 Risteli J, Niemi S, Trivedi P, Mäentausta O, Mowat A P, Risteli L. Rapid equilibrium radioimmunoassay for the amino-terminal propeptide of human type III procollagen.  Clin Chem. 1988;  34 715-718
    PubMedGoogle Scholar
  • 24 Rosendal L, Langberg H, Flyvbjerg A, Frystyk J, Orskov H, Kjaer M. Physical capacity influences the response of insulin-like growth factor and its binding proteins to training.  J Appl Physiol. 2002;  93 1669-1675
    PubMedGoogle Scholar
  • 25 Saggese G, Baroncelli G I, Bertollini S, Cinquanta L, DiNero G. Twenty-four-hour osteocalcin, carboxyterminal propeptide of type I procollagen, and aminoterminal propeptide of type III procollagen rhythms in normal and growth-retarded children.  Pediatr Res. 1994;  35 409-415
    PubMedGoogle Scholar
  • 26 Sartorio A, Agosti F, Marazzi N, Maffiuletti N A, Cella S G, Rigamonti A E, Guidetti L, Di Luigi L, Muller E E. Combined evaluation of resting IGF‐I, N-terminal propeptide of type III procollagen (PIIINP) and C-terminal cross-linked telopeptide of type I collagen (ICTP) levels might be useful for detecting inappropriate GH administration in athletes: a preliminary report.  Clin Endocrinol. 2004;  61 487-493
    CrossrefPubMedGoogle Scholar
  • 27 Sartorio A, Marazzi N, Agosti F, Faglia G, Corradini C, De Palo E, Cella S G, Rigamonti A E, Muller E E. Elite volunteer athletes of different sport disciplines may have elevated baseline GH levels divorced from unaltered levels of both IGF‐I and GH-dependent bone and collagen markers: A study on-the-field.  J Endocrinol Invest. 2004;  27 410-415
    PubMedGoogle Scholar
  • 28 Schumacher Y O, Jankovits R, Bültermann D, Schmidt A, Berg A. Hematological indices in elite cyclists.  Scand J Med Sci Sports. 2002;  12 301-308
    CrossrefPubMedGoogle Scholar
  • 29 Schwarz A J, Brasel J A, Hintz R L, Mohan S, Cooper D M. Acute effect of brief low- and high-intensity exercise on circulating insulin-like growth factor (IGF) I, II, and IGF-binding protein-3 and its proteolysis in young healthy men.  J Clin Endocrinol Metab. 1996;  81 3492-3497
    CrossrefPubMedGoogle Scholar
  • 30 Skjaerbaek C, Frystyk J, Kaal A, Laursen T, Moller J, Weeke J, Jorgensen J OL, Christiansen J S, Orskov H. Circadian variation in serum free and total insulin-like growth factor (IGF)-I and IGF‐II in untreated and treated acromegaly and growth hormone deficiency.  Clin Endocrinol. 2000;  52 25-33
    CrossrefPubMedGoogle Scholar
  • 31 Snow C M, Rosen C J, Robinson T L. Serum IGF‐I is higher in gymnasts than runners and predicts bone and lean mass.  Med Sci Sports Exerc. 2000;  32 1902-1907
    PubMedGoogle Scholar
  • 32 Strasburger C J, Bidlingmaier M, Wu Z, Morrison K M. Normal values of insulin-like growth factor I and their clinical utility in adults.  Horm Res. 2001;  55 100-105
    CrossrefPubMedGoogle Scholar
  • 33 Suikkari A-M, Sane T, Seppala M, Yki-Jarvinen H, Karonen S ‐L, Koivisto V A. Prolonged exercise increases serum insulin-like growth factor-binding protein concentrations.  J Clin Endocrinol Metab. 1989;  68 141-144
    PubMedGoogle Scholar
  • 34 Takala T ES, Vuori J, Anttinen H, Väänänen K, Myllyla R. Prolonged exercise causes an increase in the activity of galactosylhydroxylysyl glucosyltransferase and in concentration of type III procollagen aminopropeptide in human serum.  Pflugers Arch. 1986;  407 500-503
    PubMedGoogle Scholar
  • 35 Takala T ES, Vuori J J, Rahkila P J, Hakala E O, Karpakka J A, Alen M J, Orava Y S, Väänänen H K. Carbonic anhydrase III and collagen markers in serum following cross-country skiing.  Med Sci Sports Exerc. 1989;  21 593-597
    PubMedGoogle Scholar
  • 36 Virtanen P, Viitasalo J T, Vuori J, Väänänen K, Takala T ES. Effect of concentric exercise on serum muscle and collagen markers.  J Appl Physiol. 1993;  75 1272-1277
    PubMedGoogle Scholar
  • 37 Wallace J D, Cuneo R C, Baxter R, Orskov H, Keay N, Pentecost C, Dall R, Rosen T, Jorgensen J O, Cittadini A, Longobardi S, Sacca L, Christiansen J S, Bengtsson B A, Sonksen P H. Responses of the growth hormone (GH) and insulin-like growth factor axis to exercise, GH administration, and GH withdrawal in trained adult males: a potential test for GH abuse in sport.  J Clin Endocrinol Metab. 1999;  84 3591-3601
    CrossrefPubMedGoogle Scholar
  • 38 Wallace J D, Cuneo R C, Lundberg P A, Rosen T, Jorgensen J O, Longobardi S, Keay N, Sacca L, Christiansen J S, Bengtsson B A, Sonksen P H. Responses of markers of bone and collagen turnover to exercise, growth hormone (GH) administration, and GH withdrawal in trained adult males.  J Clin Endocrinol Metab. 2000;  85 124-133
    CrossrefPubMedGoogle Scholar
  • 39 Zofkova I. Pathophysiological and clinical importance of insulin-like growth factor-I with respect to bone metabolism.  Physiol Res. 2003;  52 657-679
    PubMedGoogle Scholar

PhD Jordi Segura

Pharmacology Research Unit
Institut Municipal d'Investigació Mèdica (IMIM)

Doctor Aiguader 80

08003 Barcelona

Spain

Phone: + 34 932211009

Fax: + 34 93 22 13 237

Email: jsegura@imim.es

      >