Indirect evidence of hormone abuse. Proof of doping?
Tóm tắt
Besides anabolic steroids, the most common performance-enhancing hormones are erythropoietin (EPO), insulin, GH, and gonadotropins, mostly indistinguishable from endogenous hormones and with very short half-life. This makes virtually impossible to demonstrate their use by measuring their concentration in the blood or urine. A possible approach to the problem may lie in indirect demonstration through detection of the biological effects of these substances. The finding of an increased hematocrit level is suspicious but not clearly demonstrative of EPO abuse. Very high levels of circulating EPO could be associated with a strong suspicion of doping, when associated to other abnormal parameters, such as Ht, sTFRr, EPO, RDW. The presence of antibodies against the polysaccharide fraction of lateral chains of EPO has been observed only in patients treated with rhEPO. Owing to the pulsatile pattern of GH, particularly during physical exercise, pathologically high values may be found in normal subjects. Therefore, as in the case of EPO, evidence of GH abuse can be gathered only indirectly by detecting the biological effects of its administration. In training subjects GH treatment increased GH, IGF-I, IGFBP-3 and ALS, and decreased IGBP-2. After cessation of treatment IGF-I, IGFBP-3 and ALS approached basal values between 49 and 96 h. Also the bone parameters PICP ICIP, PIUP and osteocalcin increased significantiy. Four days after cessation of treatment, levels of PIIIP and ICTP were still abnormally elevated. In conclusion, increases in IGF-I, IGFBP-3, ALS, PIIIP and ICTP are all indicative of recent GH abuse or of acromegaly.
Tài liệu tham khảo
Gore CJ, Parisotto R, Ashenden MJ, et al. Second-generation blood tests to detect erythropoietin abuse by athletes. Haematologica 2003, 88: 333–44.
Parisotto R, Wu M, Ashenden MJ, et al. Detection of recombinant human erythropoietin abuse in athletes utilizing markers of altered erythropoiesis. Haematologica 2001, 86: 128–37.
Castelli G, Famularo A, Semino C, et al. Detection of an-ti-erythropoietin antibodies in haemodialysis patients treated with recombinant human-erythropoietin. Pharmacol Res 2000, 41: 313–8.
Wallace JD, Cuneo RC, Bidlingmaier M, et al. Changes in non-22-kilodalton (kDa) isoforms of growth hormone (GH) after administration of 22-kDa recombinant human GH in trained adult males. J Clin Endocrinol Metab 2001, 86: 1731–7.
Wallace JD, Cuneo RC, Bidlingmaier M, et al. The response of molecular isoforms of growth hormone to acute exercise in trained adult males. J Clin Endocrinol Metab 2001, 86: 200–6.
Schalch DS. The influence of physical stress and exercise on growth hormone and insulin secretion in man. J Lab Clin Med 1967, 69: 256–69.
Nguyen UN, Mougin F, Simon-Rigaud ML, Rouillon JD, Marguet P, Regnard J. Influence of exercise duration on serum insulin-like growth factor and its binding proteins in athletes. Eur J Appl Physiol Occup Physiol 1998, 78: 533–7.
Chadan, SG, Dill RP, Vanderhoek K, Parkhouse WS. Influence of physical activity on plasma insulin-like growth factor-1 and insulin-like growth factor binding proteins in healthy older women. Mech Ageing Dev 1999, 109: 21–34.
De Palo EF, Gatti R, Lancerin F, Cappellin E, Sartorio A, Spinella P. The measurement of insulin-like growth factor-I (IGF-I) concentration in random urine samples. Clin Chem Lab Med 2002, 40: 574–8.
De Palo EF, Gatti R, Lancerin F, et al. Urinary insulin-like growth factor I in athletes, before and after physical exercise, and in sedentary subjects. Clin Chim Acta 2002, 322: 51–7.
Ehrnborg C, Lange KH, Dall R, et al. 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.
Wallace JD, Cuneo RC, Baxter R, et al. 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: 3591–601.
Wallace JD, Cuneo RC, Lundberg PA, et al. 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: 124–33.
Karila T, Koistinen H, Seppala M, Koistinen R, Seppala T. Growth hormone induced increase in serum IGFBP-3 level is reversed by anabolic steroids in substance abusing power athletes. Clin Endocrinol (Oxf) 1998, 49: 459–63.
Kam GY, Leung KC, Baxter RC, Ho KK. Estrogens exert route- and dose-dependent effects on insulin-like growth factor (IGF)-binding protein-3 and the acid-labile subunit of the IGF ternary complex. J Clin Endocrinol Metab 2000, 85: 1918–22.
Isley WL, Underwood LE, Clemmons DR. Dietary components that regulate serum somatomedin-C concentrations in humans. J Clin Invest 1983, 71: 175–82.
Clemmons DR, Seek MM, Underwood LE. Supplementa essential amino acids augment the somatomedin-C/insulin-ike growth factor I response to refeeding after fasting. Metabolism 1985, 34: 391–5.
Musey VC, Goldstein S, Farmer PK, Moore PB, Phillips LS. Differential regulation of IGF-I and IGF-binding protein-1 by dietary composition in humans. Am J Med Sci 1993, 305: 131–8.