Cellular and molecular mechanisms responsible for the action of testosterone on human skeletal muscle. A basis for illegal performance enhancement

British Journal of Pharmacology

Volumn 154, Issue 3, 2008, Pages 522-528

  Kadi, F ^a  

^a ÖREBRO UNIVERSITY   (Sweden)

Author keywords

Anabolic steroids; Androgen receptor; Exercise training; Hyperplasia; Hypertrophy; Muscle fibre; Myonuclei; Protein synthesis; Regeneration; Satellite cells

Indexed keywords

ANDROGEN RECEPTOR; EPITESTOSTERONE; GONADORELIN DERIVATIVE; OXENDOLONE; PLACEBO; STEROID; TESTOSTERONE; TESTOSTERONE ENANTATE;

ADIPOCYTE; ATHLETE; CELL DIFFERENTIATION; CELL NUCLEUS; CELL PROLIFERATION; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; DAUGHTER CELL; DOSE RESPONSE; DRUG ABUSE; DRUG MECHANISM; HUMAN; MUSCLE HYPERTROPHY; MUSCLE MASS; MUSCLE REGENERATION; MUSCLE STRENGTH; MUSCLE TRAINING; MYOTUBE; NONHUMAN; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN SYNTHESIS; RANDOMIZED CONTROLLED TRIAL; REVIEW; SATELLITE CELL; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; UNSPECIFIED SIDE EFFECT; URINALYSIS;

ANDROGENS; ATHLETIC PERFORMANCE; DOPING IN SPORTS; HUMANS; MUSCLE STRENGTH; MUSCLE, SKELETAL; RECEPTORS, ANDROGEN; SUBSTANCE ABUSE DETECTION; TESTOSTERONE;

EID: 44349115503     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1038/bjp.2008.118     Document Type: Review

References (52)

1. Aguilera R, Chapman TE, Starcevic B, Hatton CK, Catlin DH (2001). Performance characteristics of a carbon isotope ratio method for detecting doping with testosterone based on urine diols: controls and athletes with elevated testosterone/epitestosterone ratios. Clin Chem 47: 292-300.
2. Arner P (2005). Effects of testosterone on fat cell lipolysis. Species differences and possible role in polycystic ovarian syndrome. Biochimie 87: 39-43.
3. Bamman MM, Shipp JR, Jiang J, Gower BA, Hunter GR, Goodman A et al. (2001). Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans. Am J Physiol Endocrinol Metab 280: 383-390.
4. Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J et al. (1996). The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med 335: 1-7.
5. Bhasin S, Woodhouse L, Casaburi R, Singh AB, Bhasin D, Berman N et al. (2001). Testosterone dose-response relationships in healthy young men. Am J Physiol 281: 1172-1181.
6. Blazevich AJ, Giorgi A (2001). Effect of testosterone administration and weight training on muscle architecture. Med Sci Sports Exerc 33: 1688-1693.
7. Cheek DB (1985). The control of cell mass and replication. The DNA unit - a personal 20-year study. Early Hum Dev 12: 211-239.
8. Conboy IM, Rando TA (2002). The regulation of Notch signaling controls satellite cell activation and cell fate determination in postnatal myogenesis. Dev Cell 3: 397-409.
9. De Pergola G (2000). The adipose tissue metabolism: role of testosterone and dehydroepiandrosterone. Int J Obes Relat Metab Disord 24 (Suppl 2): S59-S63.
10. Deschenes MR, Maresh CM, Armstrong LE, Covault J, Kraemer WJ, Crivello JF (1994). Endurance and resistance exercise induce muscle fiber type specific responses in androgen binding capacity. J Steroid Biochem Mol Biol 50: 175-179.
11. Doumit ME, Cook DR, Merkel RA (1996). Testosterone up-regulates androgen receptors and decreases differentiation of porcine myogenic satellite cells in vitro. Endocrinology 137: 1385-1394.
12. Eriksson A, Kadi F, Malm C, Thornell LE (2005). Skeletal muscle morphology in power-lifters with and without anabolic steroids. Histochem Cell Biol 124: 167-175.
13. Estrada M, Espinosa A, Müller M, Jaimovich E (2003). Testosterone stimulates intracellular calcium release and mitogen-activated protein kinases via a G protein-coupled receptor in skeletal muscle cells. Endocrinology 144: 3586-3597.
14. Estrada M, Varshney A, Ehrlich BE (2006). Elevated testosterone induces apoptosis in neuronal cells. J Biol Chem 281: 25492-25501.
15. Ferrando AA, Sheffield-Moore M, Yeckel CW, Gilkison C, Jiang J, Achacosa A et al. (2002). Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Am J Physiol 282: 601-607.
16. Ferrando AA, Tipton KD, Doyle D, Phillips SM, Cortiella J, Wolfe RR (1998). Testosterone injection stimulates net protein synthesis but not tissue amino acid transport. Am J Physiol 275: 864-871.
17. Friedl KE, Dettori JR, Hannan CJ, Patience TH, Plymate SR (1991). Comparison of the effects of high dose testosterone and 19-nortestosterone to a replacement dose of testosterone on strength and body composition in normal men. J Steroid Biochem Mol Biol 40: 607-612.
18. Giorgi A, Weatherby RP, Murphy PW (1999). Muscular strength, body composition and health responses to the use of testosterone enanthate: a double blind study. J Sci Med Sport 2: 341-355.
19. Hartgens F, Kuipers H (2004). Effects of androgenic-anabolic steroids in athletes. Sports Med 34: 513-554.
20. Hartgens F, Kuipers H, Wijnen JA, Keizer HA (1996). Body composition, cardiovascular risk factors and liver function in long-term androgenic-anabolic steroids using bodybuilders three months after drug withdrawal. Int J Sports Med 17: 429-433.
21. Inoue K, Yamasaki S, Fushiki T, Okada Y, Sugimoto E (1994). Androgen receptor antagonist suppresses exercise-induced hypertrophy of skeletal muscle. Eur J Appl Physiol Occup Physiol 69: 88-91.
22. Janssen PJ, Brinkmann AO, Boersma WJ, Van der Kwast TH (1994). Immunohistochemical detection of the androgen receptor with monoclonal antibody F39.4 in routinely processed, paraffin-embedded human tissues after microwave pre-treatment. J Histochem Cytochem 42: 1169-1175.
23. Kadi F (2000). Adaptation of human skeletal muscle to training and anabolic steroids. Acta Physiol Scand 646: 1-52.
24. Kadi F (2005). Hormonal and growth factor-related mechanisms involved in the adaptation of skeletal muscle to exercise. In: Kraemer W, Rogol A (eds). The endocrine System in Sports and Exercise. Olympic Encyclopaedia of Sports Medicine vol. XI, Chapter 22. Blackwell: Massachusetts, USA, pp 306-318.
25. Kadi F, Bonnerud P, Eriksson A, Thornell LE (2000). The expression of androgen receptors in human neck and limb muscles: effects of training and self-administration of androgenic-anabolic steroids. Histochem Cell Biol 113: 25-29.
26. Kadi F, Charifi N, Denis C, Lexell J (2004a). Satellite cells and myonuclei in young and elderly women and men. Muscle Nerve 29: 120-127.
27. Kadi F, Charifi N, Denis C, Lexell J, Andersen JL, Schjerling P et al. (2005). The behaviour of satellite cells in response to exercise: what have we learned from human studies? Pflugers Arch 451: 319-327.
28. Kadi F, Charifi N, Henriksson J (2006). The number of satellite cells in slow and fast fibres from human vastus lateralis muscle. Histochem Cell Biol 126: 83-87.
29. Kadi F, Eriksson A, Holmner S, Thornell L-E (1999). Effects of anabolic steroids on the muscle cells of strength-trained athletes. Med Sci Sports Exerc 31: 1528-1534.
30. Kadi F, Schjerling P, Andersen LL, Charifi N, Madsen JL, Christensen LR et al. (2004b). The effects of heavy resistance training and detraining on satellite cells in human skeletal muscles. J Physiol 558: 1005-1012.
31. Kochakian CD, Tillotson C (1957). Influence of several C19-steroids on the growth of individual muscles of the guinea pig. Endocrinology 60: 607-618.
32. Krieg M (1976). Characterization of the androgen receptor in the skeletal muscle of the rat. Steroids 28: 261-274.
33. Kvorning T, Andersen M, Brixen K, Madsen K (2006). Suppression of endogenous testosterone production attenuates the response to strength training: a randomized, placebo-controlled, and blinded intervention study. Am J Physiol 291: 1325-1332.
34. Kvorning T, Andersen M, Brixen K, Schjerling P, Suetta C, Madsen K (2007). Suppression of testosterone does not blunt mRNA expression of myoD, myogenin, IGF, myostatin or androgen receptor post strength training in humans. J Physiol 578: 579-593.
35. Luke M, Coffey D (1994). The male accessory tissues: structure, androgen, and physiology. In: Knobil E, Neill J (eds). The Physiology of the Reproduction. Raven Press: New York, pp 1435-1488.
36. Mackey AL, Kjaer M, Dandanell Jorgensen S, Mikkelsen KH, Holm L, Dossing S et al. (2007). The influence of anti-inflammatory medication on exercise-induced myogenic precursor cell responses in humans. J Appl Physiol 103: 425-431.
37. Mauras N, Hayes V, Welch S, Rini A, Helgeson K, Dokler M et al. (1998). Testosterone deficiency in young men: marked alterations in whole body protein kinetics, strength, and adiposity. J Clin Endocrinol Metab 83: 1886-1892.
38. Mauro A (1961). Satellite cell of skeletal muscle fibers. J Biophys Biochem Cytol 9: 493-495.
39. Moss FP, Leblond CP (1971). Satellite cells as the source of nuclei in muscles of growing rats. Anat Rec 170: 421-435.
40. Petrella J, Kim J, Cross J, Kosek D, Bamman M (2006). Efficacy of myonuclear addition may explain differential myofiber growth among resistance-trained young and older men and women. Am J Physiol Endocrinol Metab 291: 937-946.
41. Powers ML, Florini JR (1975). A direct effect of testosterone on muscle cells in tissue culture. Endocrinology 97: 1043-1047.
42. Ruizeveld de Winter JA, Trapman J, Vermey M, Mulder E, Zegers ND, van der Kwast TH (1991). Androgen receptor expression in human tissues: an immunohistochemical study. J Histochem Cytochem 39: 927-936.
43. Shackleton CH, Phillips A, Chang T, Li Y (1997). Confirming testosterone administration by isotope ratio mass spectrometric analysis of urinary androstanediols. Steroids 62: 379-387.
44. Singh R, Artaza J, Taylor W, Gonzalez-Cadavid N, Bhasin S (2003). Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology 144: 5081-5088.
45. Sinha-Hikim I, Artaza J, Woodhouse L, Gonzalez-Cadavid N, Singh AB, Lee MI et al. (2002). Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy. Am J Physiol 283: 154-164.
46. Sinha-Hikim I, Cornford M, Gaytan H, Lee ML, Bhasin S (2006). Effects of testosterone supplementation on skeletal muscle fiber hypertrophy and satellite cells in community-dwelling older men. J Clin Endocrinol Metab 91: 3024-3033.
47. Sinha-Hikim I, Roth SM, Lee MI, Bhasin S (2003). Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. Am J Physiol 285: 197-205.
48. Sinha-Hikim I, Taylor WE, Gonzalez-Cadavid NF, Zheng W, Bhasin S (2004). Androgen receptor in human skeletal muscle and cultured muscle satellite cells: up-regulation by androgen treatment. J Clin Endocrinol Metab 89: 5245-5255.
49. Sottas PE, Saudan C, Schweizer C, Baume N, Mangin P, Saugy M (2008). From population- to subject-based limits of T/E ratio to detect testosterone abuse in elite sports. Forensic Sci Int 174: 166-172.
50. WADA (2004). Technical document: reporting and evaluation guidance for testosterone, epitestosterone, T/E ratio and other endogenous steroids. Available at http://www.wada-ama.org.
51. Wilson JD (1988). Androgen abuse by athletes. Endocr Rev 9: 181-199.
52. Yesalis CE (ed). (1993). Incidence of anabolic steroid use: a discussion of methodological issues. Anabolic Steroids in Sport and Exercise. Human kinetics: champaign, IL, USA, pp 49-69.