Anabolic-androgenic steroid does not enhance compensatory muscle hypertrophy but significantly diminish muscle damages in the rat surgical ablation model

Tamaki, Toru; Uchiyama, Yoshiyasu; Okada, Yoshinori; Tono, Kayoko; Nitta, Masahiro; Hoshi, Akio; Akatsuka, Akira

doi:10.1007/s00418-009-0584-2

Cited by 16 publications

(24 citation statements)

References 31 publications

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“…An alternative explanation for our finding is that the growth stimulus provided by SA was insufficient and was below some threshold requiring satellite cells, resulting in a false-negative, type II error. We think that this is an unlikely possibility given that SA has been shown to induce a maximal hypertrophic response that, in our hands, resulted in a twofold increase in muscle mass within two weeks (Tamaki et al, 2009a). The significant increase in Pax7 + cells, myonuclei per fiber and BrdU + positive myonuclei in the vehicle-treated group are in agreement with previous studies and support the view that satellite cells are involved in the hypertrophic response induced by SA (Akiho et al, 2010;Ishido et al, 2009).…”

Section: Research Articlesupporting

confidence: 92%

“…The growth response induced by SA is considered to be maximal as even the administration of an anabolic androgen failed to enhance the degree of hypertrophy (Tamaki et al, 2009a). Furthermore, it is well documented that SA induces satellite cell proliferation and the accretion of 'new', BrdU + myonuclei, presumably derived from the fusion of satellite cells (Ishido et al, 2009;Westerkamp and Gordon, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Effective fiber hypertrophy in satellite cell-depleted skeletal muscle

et al. 2011

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SUMMARYAn important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca 2+ sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells.

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Section: Research Articlesupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Effective fiber hypertrophy in satellite cell-depleted skeletal muscle

et al. 2011

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“…per week was much higher than the FDA-recommended analogous dosage for a human, 59 but comparable to the dosages used in other animal studies (5.6 mg/kg per day, 10 6 mg/kg per week, 30,32,57 3.75 mg/kg per week 53 ). Some studies, however, used even higher dosages (15 mg/ kg per week 6,54 ), and body builders are reported to use 10-100 times the normal therapeutic dosage of anabolic steroids.…”

Section: Discussionsupporting

confidence: 66%

Effects of nandrolone on recovery after neurotization of chronically denervated muscle in a rat model

Isaacs¹,

Feher²,

Shall³

et al. 2013

JNS

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F unctional recovery following major peripheral nerve injuries is often suboptimal despite appropriate and standard treatment. 2,23,27,34,44 Muscles may be reinnervated but remain too weakened to offer much functional benefit. Although a complex and multifactorial problem, time-related permanent changes to denervated muscle awaiting reinnervation play a significant role in these poor results. This process, referred to as denervation atrophy, involves loss of muscle mass, muscle fiber size, and contractile composition. 16,51 While research has progressed toward ways to improve nerve regeneration and to avoid or decrease the development of these muscle changes, our focus has been on strategies to optimize and augment the functional recovery of reinnervated muscles.Anabolic steroids, which have been shown to cause hypertrophy of normal muscle, delay atrophy in immobilized muscle, and to slow progression of denervation atrophy, 9,45,59 are an obvious candidate for this application. Promising preliminary data demonstrated improved muscle contraction recovery in anabolic steroid-treated rodents following the reversal of chronic denervation of hind limb muscles. 22 The purpose of this study was to confirm and further elucidate the role and mechanism by which anabolic steroids (nandrolone) improve strength and functional recovery in reinnervated muscles followEffects of nandrolone on recovery after neurotization of chronically denervated muscle in a rat model Object. Suboptimal recovery following repair of major peripheral nerves has been partially attributed to denervation atrophy. Administration of anabolic steroids in conjunction with neurotization may improve functional recovery of chronically denervated muscle. The purpose of this study was to evaluate the effect of the administration of nandrolone on muscle recovery following prolonged denervation in a rat model.Methods. Eight groups of female Sprague-Dawley rats (15 rats per group, 120 in all) were divided into 3-or 6-month denervated hind limb and sham surgery groups and, then, nandrolone treatment groups and sham treatment groups. Evaluation of treatment effects included nerve conduction, force of contraction, comparative morphology, histology (of muscle fibers), protein electrophoresis (for muscle fiber grouping), and immunohistochemical evaluation.Results. Although a positive trend was noted, neither reinnervated nor normal muscle showed a statistically significant increase in peak muscle force following nandrolone treatment. Indirect measures, including muscle mass (weight and diameter), muscle cell size, muscle fiber type, and satellite cell counts, all failed to support significant anabolic effect.Conclusions. There does not seem to be a functional benefit from nandrolone treatment following reinnervation of either mild or moderately atrophic muscle (related to prolonged denervation) in a rodent model. (http://thejns.org/doi/abs/10.3171/2013.5.JNS121837) key WorDs • anabolic steroid • denervation atrophy • nerve repair • rodent • muscle recovery • nand...

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“…It must be also eVective for the cells in peripheral nervous system. As supporting evidence, signiWcant increases in amino acid and thymidine uptake (Tamaki et al 2009) and the number of proliferating (positive for BrdU; 5-bromo-2Ј-deoxyuridine or PCNA; proliferating cell nuclear antigen) cells in this model have been reported (Tamaki et al , 2009. Newly myogenesis (Yamada et al 1989) and formation of branched-muscle Wbers , and increased interstitial (nonmuscle Wbers) area in the histological sections have also been reported in this model.…”

Section: Introductionmentioning

confidence: 77%

“…We recently demonstrated that this model shows near maximal responses of cellular potential in the skeletal muscle during 5-10 weeks of mechanical stretch overload, and suggested that multiple stimulation of muscle-nerve-blood vessels units (appearance of PCNA+ cells) occurs in this model (Tamaki et al 2009). Therefore, this model is considered to be suitable for analyzing physiological cellular responses in skeletal muscle totally.…”

Section: Introductionmentioning

confidence: 96%

Multiple stimulations for muscle–nerve–blood vessel unit in compensatory hypertrophied skeletal muscle of rat surgical ablation model

Tamaki

Uchiyama

Okada

et al. 2009

Histochem Cell Biol

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Tissue inflammation and multiple cellular responses in the compensatory enlarged plantaris (OP Plt) muscle induced by surgical ablation of synergistic muscles (soleus and gastrocnemius) were followed over 10 weeks after surgery. Contralateral surgery was performed in adult Wistar male rats. Cellular responses in muscle fibers, blood vessels and nerve fibers were analyzed by immunohistochemistry and electron microscopy. Severe muscle fiber damage and disappearance of capillaries associated with apparent tissue edema were observed in the peripheral portion of OP Plt muscles during the first week, whereas central portions were relatively preserved. Marked cell activation/proliferation was also mainly observed in peripheral portions. Similarly, activated myogenic cells were seen not only inside but also outside of muscle fibers. The former were likely satellite cells and the latter may be interstitial myogenic cells. One week after surgery, small muscle fibers, small arteries and capillaries and several branched-muscle fibers were evident in the periphery, thus indicating new muscle fiber and blood vessel formation. Proliferating cells were also detected in the nerve bundles in the Schwann cell position. These results indicate that the compensatory stimulated/enlarged muscle is a suitable model for analyzing multiple physiological cellular responses in muscle-nerve-blood vessel units under continuous stretch stimulation.

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Anabolic-androgenic steroid does not enhance compensatory muscle hypertrophy but significantly diminish muscle damages in the rat surgical ablation model

Cited by 16 publications

References 31 publications

Effective fiber hypertrophy in satellite cell-depleted skeletal muscle

Effective fiber hypertrophy in satellite cell-depleted skeletal muscle

Effects of nandrolone on recovery after neurotization of chronically denervated muscle in a rat model

Multiple stimulations for muscle–nerve–blood vessel unit in compensatory hypertrophied skeletal muscle of rat surgical ablation model

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