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Growth Hormone

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 195))

Abstract

Human growth hormone (hGH) is a proteohormone secreted by the pituitary gland. It acts through binding to the hGH receptor, inducing either direct effects or initiating the production of insulin-like growth-factor I (IGF-I), the most important mediator of hGH effects. Growth hormone is primarily known to promote longitudinal growth in children and adolescents, but has also various important metabolic functions throughout adult life. Effects of hGH on the adult organism are well established from studies with recombinant growth hormone (rhGH) therapy in growth hormone deficient subjects. In this particular group of patients, replacement of hGH leads to increased lipolysis and lean body mass, decreased fat mass, improvements in VO2max, and maximal power output. Although extrapolation from these findings to the situation in well trained healthy subjects is impossible, and controlled studies in healthy subjects are scarce, abuse of hGH seems to be popular among athletes trying to enhance physical performance. Detection of the application of rhGH is difficult, especially because the amino acid sequence of rhGH is identical to the major 22,000 Da isoform of hGH normally secreted by the pituitary. Furthermore, some physiological properties of hGH secretion also hindered the development of a doping test: secreted in a pulsatile manner, it has a very short half-life in circulation, which leads to highly variable serum levels. Concentration alone therefore cannot prove the exogenous administration of hGH.

Two approaches have independently been developed for the detection of hGH doping: The so-called “marker approach” investigates changes in hGH-dependent parameters like IGF-I or components of bone and collagen metabolism, which are increased after hGH injection. In contrast, the so-called “isoform approach” directly analyses the spectrum of molecular isoforms in circulation: the pituitary gland secretes a spectrum of homo- and heterodimers and – multimers of a variable spectrum of hGH isoforms, whereas rhGH consists of the monomeric 22,000 Da isoform only. This isoform therefore becomes predominant after injection of rhGH. Specific immunoassays with preference for the one or the other isoform allow analysis of the relative abundance of the 22,000 Da isoform. Application of rhGH can be proven when the ratio of this isoform relative to the others is increased above a certain threshold. Because the “marker method” and the “isoform method” have a different window of opportunity for detection, complementary use of both tests could be a way to increase the likelihood of detecting cheating athletes.

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References

  • Arsene CG, Ohlendorf R, Burkitt W, Pritchard C, Henrion A, O’Connor G, Bunk DM, Guttler B (2008) Protein quantification by isotope dilution mass spectrometry of proteolytic fragments: cleavage rate and accuracy. Anal Chem 80:4154–4160

    Article  Google Scholar 

  • Baumann G (1999) Growth hormone heterogeneity in human pituitary and plasma. Horm Res 51(Suppl 1):2–6

    Article  Google Scholar 

  • Bidlingmaier M, Strasburger CJ (2007) Technology insight: detecting growth hormone abuse in athletes. Nat Clin Pract Endocrinol Metab 3:769–777

    Article  Google Scholar 

  • Bidlingmaier M, Wu Z, Strasburger CJ (2000) Test method: GH. Baillieres Best Pract Res Clin Endocrinol Metab 14:99–109

    Article  Google Scholar 

  • Bidlingmaier M, Suhr J, Ernst A, Wu Z, Keller A, Strasburger CJ, Bergmann A (2009) High-sensitivity chemiluminescence immunoassays for detection of growth hormone doping in sports. Clin Chem 55(3):445–453

    Article  Google Scholar 

  • Bottinelli R, Narici M, Pellegrino MA, Kayser B, Canepari M, Faglia G, Sartorio A (1997) Contractile properties and fiber type distribution of quadriceps muscles in adults with childhood-onset growth hormone deficiency. J Clin Endocrinol Metab 82:4133–4138

    Article  Google Scholar 

  • Bredehoft M, Schanzer W, Thevis M (2008) Quantification of human insulin-like growth factor-1 and qualitative detection of its analogues in plasma using liquid chromatography/electrospray ionisation tandem mass spectrometry. Rapid Commun Mass Spectrom 22:477–485

    Article  Google Scholar 

  • Buijs MM, Burggraaf J, Langendonk JG, Schoemaker RC, Frolich M, Arndt JW, Cohen AF, Romijn JA, Ackermans MT, Sauerwein HP, Meinders AE, Pijl H (2002a) Hyposomatotropism blunts lipolysis in abdominally obese women. J Clin Endocrinol Metab 87:3851–3858

    Article  Google Scholar 

  • Buijs MM, Romijn JA, Burggraaf J, De Kam ML, Cohen AF, Frolich M, Stellaard F, Meinders AE, Pijl H (2002b) Growth hormone blunts protein oxidation and promotes protein turnover to a similar extent in abdominally obese and normal-weight women. J Clin Endocrinol Metab 87:5668–5674

    Article  Google Scholar 

  • Butler AA, Le Roith D (2001) Control of growth by the somatropic axis: growth hormone and the insulin-like growth factors have related and independent roles. Annu Rev Physiol 63:141–164

    Article  Google Scholar 

  • Buzzini SR (2007) Abuse of growth hormone among young athletes. Pediatr Clin North Am 54:823–843, xiii

    Google Scholar 

  • Calfee R, Fadale P (2006) Popular ergogenic drugs and supplements in young athletes. Pediatrics 117:e577–e589

    Article  Google Scholar 

  • Cittadini A, Cuocolo A, Merola B, Fazio S, Sabatini D, Nicolai E, Colao A, Longobardi S, Lombardi G, Sacca L (1994) Impaired cardiac performance in GH-deficient adults and its improvement after GH replacement. Am J Physiol 267:E219–E225

    Google Scholar 

  • Crist DM, Peake GT, Egan PA, Waters DL (1988) Body composition response to exogenous GH during training in highly conditioned adults. J Appl Physiol 65:579–584

    Google Scholar 

  • Crist DM, Peake GT, Loftfield RB, Kraner JC, Egan PA (1991) Supplemental growth hormone alters body composition, muscle protein metabolism and serum lipids in fit adults: characterization of dose-dependent and response-recovery effects. Mech Ageing Dev 58:191–205

    Article  Google Scholar 

  • Cuneo RC, Salomon F, Wiles CM, Sonksen PH (1990) Skeletal muscle performance in adults with growth hormone deficiency. Horm Res 33:55–60

    Article  Google Scholar 

  • Cuneo RC, Salomon F, Wiles CM, Hesp R, Sonksen PH (1991a) Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength. J Appl Physiol 70:688–694

    Google Scholar 

  • Cuneo RC, Salomon F, Wiles CM, Hesp R, Sonksen PH (1991b) Growth hormone treatment in growth hormone-deficient adults. II. Effects on exercise performance. J Appl Physiol 70:695–700

    Google Scholar 

  • Cuneo RC, Salomon F, Wilmshurst P, Byrne C, Wiles CM, Hesp R, Sonksen PH (1991c) Cardiovascular effects of growth hormone treatment in growth-hormone- deficient adults: stimulation of the renin-aldosterone system. Clin Sci (Colch) 81:587–592

    Google Scholar 

  • Cuneo RC, Salomon F, Wiles CM, Round JM, Jones D, Hesp R, Sonksen PH (1992) Histology of skeletal muscle in adults with GH deficiency: comparison with normal muscle and response to GH treatment. Horm Res 37:23–28

    Article  Google Scholar 

  • Dean H (2002) Does exogenous growth hormone improve athletic performance? Clin J Sport Med 12:250–253

    Article  Google Scholar 

  • Deyssig R, Frisch H, Blum WF, Waldhor T (1993) Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes. Acta Endocrinol (Copenh) 128:313–318

    Google Scholar 

  • Duchaine D (1983) Underground steroid handbook. HLR Technical Books, California

    Google Scholar 

  • Erotokritou-Mulligan I, Bassett EE, Kniess A, Sonksen PH, Holt RI (2007) Validation of the growth hormone (GH)-dependent marker method of detecting GH abuse in sport through the use of independent data sets. Growth Horm IGF Res 17:416–423

    Article  Google Scholar 

  • Erotokritou-Mulligan I, Bassett EE, Bartlett C, Cowan D, McHugh C, Seah R, Curtis B, Wells V, Harrison K, Sonksen PH, Holt RI (2008) The effect of sports injury on insulin like growth factor-I and procollagen III peptide: implications for detection of growth hormone abuse in athletes. J Clin Endocrinol Metab 93(7):2760–2763

    Article  Google Scholar 

  • Ezzat S, Fear S, Gaillard RC, Gayle C, Landy H, Marcovitz S, Mattioni T, Nussey S, Rees A, Svanberg E (2002) Gender-specific responses of lean body composition and non-gender-specific cardiac function improvement after GH replacement in GH-deficient adults. J Clin Endocrinol Metab 87:2725–2733

    Article  Google Scholar 

  • Frisch H (1999) Growth hormone and body composition in athletes. J Endocrinol Invest 22:106–109

    Google Scholar 

  • Gibney J, Wallace JD, Spinks T, Schnorr L, Ranicar A, Cuneo RC, Lockhart S, Burnand KG, Salomon F, Sonksen PH, Russell-Jones D (1999) The effects of 10 years of recombinant human growth hormone (GH) in adult GH-deficient patients. J Clin Endocrinol Metab 84:2596–2602

    Article  Google Scholar 

  • Gibney J, Healy ML, Sonksen PH (2007) The growth hormone/insulin-like growth factor-I axis in exercise and sport. Endocr Rev 28:603–624

    Article  Google Scholar 

  • Hansen TK, Gravholt CH, OR H, Rasmussen MH, Christiansen JS, Jorgensen JO (2002) Dose dependency of the pharmacokinetics and acute lipolytic actions of growth hormone. J Clin Endocrinol Metab 87:4691–4698

    Article  Google Scholar 

  • Healy ML, Russell-Jones D (1997) Growth hormone and sport: abuse, potential benefits, and difficulties in detection. Br J Sports Med 31:267–268

    Article  Google Scholar 

  • Healy ML, Dall R, Gibney J, Bassett E, Ehrnborg C, Pentecost C, Rosen T, Cittadini A, Baxter RC, Sonksen PH (2005) Toward the development of a test for growth hormone (GH) abuse: a study of extreme physiological ranges of GH-dependent markers in 813 elite athletes in the postcompetition setting. J Clin Endocrinol Metab 90:641–649

    Article  Google Scholar 

  • Holl RW, Schwarz U, Schauwecker P, Benz R, Veldhuis JD, Heinze E (1993) Diurnal variation in the elimination rate of human growth hormone (GH): the half-life of serum GH is prolonged in the evening, and affected by the source of the hormone, as well as by body size and serum estradiol. J Clin Endocrinol Metab 77:216–220

    Article  Google Scholar 

  • Hutler M, Schnabel D, Staab D, Tacke A, Wahn U, Boning D, Beneke R (2002) Effect of growth hormone on exercise tolerance in children with cystic fibrosis. Med Sci Sports Exerc 34:567–572

    Article  Google Scholar 

  • Ishikawa M, Yokoya S, Tachibana K, Hasegawa Y, Yasuda T, Tokuhiro E, Hashimoto Y, Tanaka T (1999) Serum levels of 20-kilodalton human growth hormone (GH) are parallel those of 22-kilodalton human GH in normal and short children. J Clin Endocrinol Metab 84:98–104

    Article  Google Scholar 

  • Janssen YJ, Doornbos J, Roelfsema F (1999) Changes in muscle volume, strength, and bioenergetics during recombinant human growth hormone (GH) therapy in adults with GH deficiency. J Clin Endocrinol Metab 84:279–284

    Article  Google Scholar 

  • Jenkins P (1999) Detection of doping. Lancet 353:1532

    Google Scholar 

  • Johannsson G, Grimby G, Sunnerhagen KS, Bengtsson BA (1997) Two years of growth hormone (GH) treatment increase isometric and isokinetic muscle strength in GH-deficient adults. J Clin Endocrinol Metab 82:2877–2884

    Article  Google Scholar 

  • Jorgensen JO, Thuesen L, Muller J, Ovesen P, Skakkebaek NE, Christiansen JS (1994) Three years of growth hormone treatment in growth hormone-deficient adults: near normalization of body composition and physical performance. Eur J Endocrinol 130:224–228

    Article  Google Scholar 

  • Jorgensen JO, Vahl N, Hansen TB, Thuesen L, Hagen C, Christiansen JS (1996) Growth hormone versus placebo treatment for one year in growth hormone deficient adults: increase in exercise capacity and normalization of body composition. Clin Endocrinol (Oxf) 45:681–688

    Article  Google Scholar 

  • Keller A, Wu Z, Kratzsch J, Keller E, Blum WF, Kniess A, Preiss R, Teichert J, Strasburger CJ, Bidlingmaier M (2007) Pharmacokinetics and pharmacodynamics of GH: dependence on route and dosage of administration. Eur J Endocrinol 156:647–653

    Article  Google Scholar 

  • Kniess A, Ziegler E, Kratzsch J, Thieme D, Muller RK (2003) Potential parameters for the detection of hGH doping. Anal Bioanal Chem 376:696–700

    Article  Google Scholar 

  • Lange KH, Isaksson F, Juul A, Rasmussen MH, Bulow J, Kjaer M (2000) Growth hormone enhances effects of endurance training on oxidative muscle metabolism in elderly women. Am J Physiol Endocrinol Metab 279:E989–E996

    Google Scholar 

  • Le Roith D, Bondy C, Yakar S, Liu JL, Butler A (2001) The somatomedin hypothesis: 2001. Endocr Rev 22:53–74

    Article  Google Scholar 

  • Leung KC, Howe C, Gui LY, Trout G, Veldhuis JD, Ho KK (2002) Physiological and pharmacological regulation of 20-kDa growth hormone. Am J Physiol Endocrinol Metab 283:E836–E843

    Google Scholar 

  • Longobardi S, Keay N, Ehrnborg C, Cittadini A, Rosen T, Dall R, Boroujerdi MA, Bassett EE, Healy ML, Pentecost C, Wallace JD, Powrie J, Jorgensen JO, Sacca L (2000) 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 85:1505–1512

    Article  Google Scholar 

  • Matich AJ (2007) Performance-enhancing drugs and supplements in women and girls. Curr Sports Med Rep 6:387–391

    Article  Google Scholar 

  • McHugh CM, Park RT, Sonksen PH, Holt RI (2005) Challenges in detecting the abuse of growth hormone in sport. Clin Chem 51:1587–1593

    Article  Google Scholar 

  • Merola B, Cittadini A, Colao A, Ferone D, Fazio S, Sabatini D, Biondi B, Sacca L, Lombardi G (1993) Chronic treatment with the somatostatin analog octreotide improves cardiac abnormalities in acromegaly. J Clin Endocrinol Metab 77:790–793

    Article  Google Scholar 

  • Merola B, Longobardi S, Sofia M, Pivonello R, Micco A, Di Rella F, Esposito V, Colao A, Lombardi G (1996) Lung volumes and respiratory muscle strength in adult patients with childhood- or adult-onset growth hormone deficiency: effect of 12 months’ growth hormone replacement therapy. Eur J Endocrinol 135:553–558

    Article  Google Scholar 

  • Nagulesparen M, Trickey R, Davies MJ, Jenkins JS (1976) Muscle changes in acromegaly. Br Med J 2:914–915

    Article  Google Scholar 

  • Nass R, Huber RM, Klauss V, Muller OA, Schopohl J, Strasburger CJ (1995) Effect of growth hormone (hGH) replacement therapy on physical work capacity and cardiac and pulmonary function in patients with hGH deficiency acquired in adulthood. J Clin Endocrinol Metab 80:552–557

    Article  Google Scholar 

  • Nelson AE, Howe CJ, Nguyen TV, Leung KC, Trout GJ, Seibel MJ, Baxter RC, Handelsman DJ, Kazlauskas R, Ho KK (2006) Influence of demographic factors and sport type on growth hormone-responsive markers in elite athletes. J Clin Endocrinol Metab 91:4424–4432

    Article  Google Scholar 

  • Nilsson S, Spak F, Marklund B, Baigi A, Allebeck P (2005) Attitudes and behaviors with regards to androgenic anabolic steroids among male adolescents in a county of Sweden. Subst Use Misuse 40:1–12

    Article  Google Scholar 

  • Ohlsson C, Bengtsson BA, Isaksson OG, Andreassen TT, Slootweg MC (1998) Growth hormone and bone. Endocr Rev 19:55–79

    Article  Google Scholar 

  • Pichard C, Kyle U, Chevrolet JC, Jolliet P, Slosman D, Mensi N, Temler E, Ricou B (1996) Lack of effects of recombinant growth hormone on muscle function in patients requiring prolonged mechanical ventilation: a prospective, randomized, controlled study. Crit Care Med 24:403–413

    Article  Google Scholar 

  • Powrie JK, Bassett EE, Rosen T, Jorgensen JO, Napoli R, Sacca L, Christiansen JS, Bengtsson BA, Sonksen PH (2007) Detection of growth hormone abuse in sport. Growth Horm IGF Res 17:220–226

    Article  Google Scholar 

  • Rennie MJ (2003) Claims for the anabolic effects of growth hormone: a case of the emperor’s new clothes? Br J Sports Med 37:100–105

    Article  Google Scholar 

  • Rickert VI, Pawlak-Morello C, Sheppard V, Jay MS (1992) Human growth hormone: a new substance of abuse among adolescents? Clin Pediatr (Phila) 31:723–726

    Article  Google Scholar 

  • Russell JA (1957) Effects of growth hormone on protein and carbohydrate metabolism. Am J Clin Nutr 5:404–416

    Google Scholar 

  • Salomon F, Cuneo RC, Hesp R, Sonksen PH (1989) The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med 321:1797–1803

    Article  Google Scholar 

  • Sartorio A, Narici M, Conti A, Monzani M, Faglia G (1995) Quadriceps and hand-grip strength in adults with childhood-onset growth hormone deficiency. Eur J Endocrinol 132:37–41

    Article  Google Scholar 

  • Saugy M, Robinson N, Saudan C, Baume N, Avois L, Mangin P (2006) Human growth hormone doping in sport. Br J Sports Med 40(Suppl 1):i35–i39

    Article  Google Scholar 

  • Schoemaker RC, Buijs MM, Pijl H, Burggraaf J, Cohen AF (2002) Modeling the influence of growth hormone on lipolysis. J Pharmacokinet Pharmacodyn 29:157–170

    Article  Google Scholar 

  • Shalet SM, Toogood A, Rahim A, Brennan BM (1998) The diagnosis of growth hormone deficiency in children and adults. Endocr Rev 19:203–223

    Article  Google Scholar 

  • Taaffe DR, Jin IH, Vu TH, Hoffman AR, Marcus R (1996) Lack of effect of recombinant human growth hormone (GH) on muscle morphology and GH-insulin-like growth factor expression in resistance-trained elderly men. J Clin Endocrinol Metab 81:421–425

    Article  Google Scholar 

  • Thevis M, Bredehöft M, Kohler M, Schänzer W (2009) Mass spectrometry-based analysis of IGF-1 and hGH. Handbook of Experimental Pharmacology, this volume

    Google Scholar 

  • Wallace JD, Cuneo RC (2000) Growth hormone and sport. Int Growth Monit 10:2–6

    Google Scholar 

  • Wallace JD, Cuneo RC, Baxter R, Orskov H, Keay N, Pentecost C, Dall R, Rosen T, Jorgensen JO, Cittadini A, Longobardi S, Sacca L, Christiansen JS, Bengtsson BA, Sonksen PH (1999) 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 84:3591–3601

    Article  Google Scholar 

  • Wallace JD, Cuneo RC, Lundberg PA, Rosen T, Jorgensen JO, Longobardi S, Keay N, Sacca L, Christiansen JS, Bengtsson BA, Sonksen PH (2000) 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 85:124–133

    Article  Google Scholar 

  • Wallace JD, Cuneo RC, Bidlingmaier M, Lundberg PA, Carlsson L, Boguszewski CL, Hay J, Boroujerdi M, Cittadini A, Dall R, Rosen T, Strasburger CJ (2001a) 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 86:1731–1737

    Article  Google Scholar 

  • Wallace JD, Cuneo RC, Bidlingmaier M, Lundberg PA, Carlsson L, Boguszewski CL, Hay J, Healy ML, Napoli R, Dall R, Rosen T, Strasburger CJ (2001b) The response of molecular isoforms of growth hormone to acute exercise in trained adult males. J Clin Endocrinol Metab 86:200–206

    Article  Google Scholar 

  • Wolf E, Wanke R, Schenck E, Hermanns W, Brem G (1995) Effects of growth hormone overproduction on grip strength of transgenic mice. Eur J Endocrinol 133:735–740

    Article  Google Scholar 

  • World Anti Doping Agency (2009) The World Anti-Doping Code, International Standard Laboratories, http://www.wada-ama.org/rtecontent/document/International_Standard_for_Laboratories_v6_0_January_2009.pdf. Cited 6 February 2009

  • Wu Z, Bidlingmaier M, Dall R, Strasburger CJ (1999) Detection of doping with human growth hormone. Lancet 353:895

    Article  Google Scholar 

  • Wu Z, Bidlingmaier M, Strasburger CJ (2002) Development of human growth hormone (hGH) isoform specific antibodies and their use in a possible test to detect hGH-doping in sports [abstract]. 84th Meeting of the Endocrine Society, San Francis

    Google Scholar 

  • Yarasheski KE, Campbell JA, Smith K, Rennie MJ, Holloszy JO, Bier DM (1992) Effect of growth hormone and resistance exercise on muscle growth in young men. Am J Physiol 262:E261–E267

    Google Scholar 

  • Yarasheski KE, Zachweija JJ, Angelopoulos TJ, Bier DM (1993) Short-term growth hormone treatment does not increase muscle protein synthesis in experienced weight lifters. J Appl Physiol 74:3073–3076

    Google Scholar 

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Bidlingmaier, M., Strasburger, C.J. (2010). Growth Hormone. In: Thieme, D., Hemmersbach, P. (eds) Doping in Sports: Biochemical Principles, Effects and Analysis. Handbook of Experimental Pharmacology, vol 195. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-79088-4_8

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