Phosphorylation of p70s6 kinase is implicated in androgen-induced levator ani muscle anabolism in castrated rats

Xu, T.; Shen, Ying; Pink, Heather M.; Triantafillou, Jim; Stimpson, Stephen A.; Turnbull, Philip; Han, Bajin

doi:10.1016/j.jsbmb.2004.07.008

Cited by 27 publications

(38 citation statements)

References 45 publications

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“…As yet no data have been generated demonstrating a distinction in dynamics of specific IGF-I isoforms upon androgen administration. Androgenic activity may be directly linked to the IGF-I signalling system with p70s6kinase, found downstream of the Akt/mTOR pathway, a candidate for early evidence is emerging (Xu et al 2004). A proportion of the anabolic effects of androgens may also be anti-catabolic via an anti-glucocorticoid action (Danhaive & Rousseau 1988, Zhao et al 2004.…”

Section: Mechanisms Of Androgen Actionmentioning

confidence: 99%

Modifying muscle mass – the endocrine perspective

Solomon

Bouloux

2006

Journal of Endocrinology

143

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This review describes the major hormonal factors that determine the balance between human skeletal muscle anabolism and catabolism in health and disease, with specific reference to age-related muscle loss (sarcopenia). The molecular mechanisms associated with muscle hypertrophy are described, and the central role of the satellite cell highlighted. The biological dynamics of satellite cells, varying between states of quiescence, proliferation and differentiation are strongly influenced by local endocrine factors. The molecular mechanisms of muscle atrophy are examined focussing on the causes of sarcopenia and associations with systemic medical disorders. In addition, evidence is provided that the mechanisms of atrophy and hypertrophy are unlikely to be simple opposites. Novel endocrine mechanisms underpinning mechanotransduction include IGF-I subtypes that may differentiate between endocrine and mechanical signals; their interaction with classical endocrine factors is an active area of translational research. Recently acquired knowledge on the mechanism of anabolic effects of androgens is also reviewed. The increasingly recognised role of myostatin, a negative regulator of muscle function, is described, as well as its potential as a therapeutic target. Strategies to counter age-related sarcopenia thus represent an exciting field of future investigation.

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Section: Mechanisms Of Androgen Actionmentioning

confidence: 99%

Modifying muscle mass – the endocrine perspective

Solomon

Bouloux

2006

Journal of Endocrinology

143

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“…Other potential mechanisms are suggested by findings from studies in hypogonadal men that have shown that testosterone upregulates the muscle growth factor insulin-like growth factor -1 (IGF-1; Ferrando et al, 2002;Urban et al, 1995). Additionally, in hypogonadal rodents, testosterone has been found to activate a downstream target of IGF-1, mTOR (Xu et al, 2004).…”

mentioning

confidence: 99%

Nandrolone Normalizes Determinants of Muscle Mass and Fiber Type after Spinal Cord Injury

Zhao²,

Zhao³

et al. 2012

Journal of Neurotrauma

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Spinal cord injury (SCI) results in atrophy of skeletal muscle and changes from slow oxidative to fast glycolytic fibers, which may reflect reduced levels of peroxisome proliferator-activated receptor gamma coactivator-1a (PGC-1a), increased myostatin signaling, or both. In animals, testosterone reduces loss of muscle fiber crosssectional area and activity of enzymes of energy metabolism. To identify the molecular mechanisms behind the benefits of androgens on paralyzed muscle, male rats were spinal cord transected and treated for 8 weeks with vehicle, testosterone at a physiological replacement dose, or testosterone plus nandrolone, an anabolic steroid. Treatments were initiated immediately after SCI and continued until the day animals were euthanized. In the SCI animals, gastrocnemius muscle mass was significantly increased by testosterone plus nandrolone, but not by testosterone alone. Both treatments significantly reduced nuclear content of Smad2/3 and mRNA levels of activin receptor IIB and follistatin-like 3. Testosterone alone or with nandrolone reversed SCI-induced declines in cellular and nuclear levels of PGC-1a protein and PGC-1a mRNA levels. For PGC-1a target genes, testosterone plus nandrolone partially reversed SCI-induced decreases in levels of proteins without corresponding increases in their mRNA levels. Thus, the findings demonstrate that following SCI, signaling through activin receptors and Smad2/3 is increased, and that androgens suppress activation of this signaling pathway. The findings also indicate that androgens upregulate PGC-1a in paralyzed muscle and promote its nuclear localization, but that these effects are insufficient to fully activate transcription of PGC-1a target genes. Furthermore, the transcription of these genes is not tightly coupled with their translation.

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“…Indeed, androgen treatment was found to increase IGF-I mRNA in bovine satellite cells [156] as well as in rat diaphragmatic muscle [19]. In addition, levels of IGF binding proteins (IGFBPs) were dramatically suppressed [155]. The presence of two AREs in the upstream promoter of the IGF-I gene [157] supports this hypothesis.…”

Section: Crosstalk Between Igf-i and Androgensmentioning

confidence: 90%

“…However, circulating GH and IGF-I may not be essential for the anabolic effects of androgens, as testosterone increases total body weight and LA muscle mass even in hypophysectomized rats that are deficient in GH and low in IGF-I serum levels [154]. Moreover, administration of high doses of dihydrotestosterone to orchidectomized rats did not change serum IGF-I concentrations although LA weight was restored to sham levels [155], and in ARKO male mice, serum IGF-I was not different from wild-type animals [59]. Collectively, these data suggest that circulating GH and IGF-I play only a minor role in mediating the anabolic effects of androgens.…”

Section: Crosstalk Between Igf-i and Androgensmentioning

confidence: 96%

“…The ribosomal protein kinase p70 s6k is a downstream effector of IGF-I participating in the regulation of protein turnover in skeletal muscle [159]. Dihydrotestosterone was shown to induce phosphorylation of p70 s6k in LA muscle of orchidectomized rats in a dosedependent manner [155]. The phosphorylation status of p70 s6k was decreased by the AR antagonist flutamide, suggesting that activation of intramuscular IGF-I signaling by androgens is AR-mediated.…”

Section: Crosstalk Between Igf-i and Androgensmentioning

confidence: 99%

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Androgens and skeletal muscle: cellular and molecular action mechanisms underlying the anabolic actions

Dubois

Laurent

Boonen

et al. 2011

Cell. Mol. Life Sci.

143

111

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Androgens increase both the size and strength of skeletal muscle via diverse mechanisms. The aim of this review is to discuss the different cellular targets of androgens in skeletal muscle as well as the respective androgen actions in these cells leading to changes in proliferation, myogenic differentiation, and protein metabolism. Androgens bind and activate a specific nuclear receptor which will directly affect the transcription of target genes. These genes encode muscle-specific transcription factors, enzymes, structural proteins, as well as microRNAs. In addition, anabolic action of androgens is partly established through crosstalk with other signaling molecules such as Akt, myostatin, IGF-I, and Notch. Finally, androgens may also exert non-genomic effects in muscle by increasing Ca(2+) uptake and modulating kinase activities. In conclusion, the anabolic effect of androgens on skeletal muscle is not only explained by activation of the myocyte androgen receptor but is also the combined result of many genomic and non-genomic actions.

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Phosphorylation of p70s6 kinase is implicated in androgen-induced levator ani muscle anabolism in castrated rats

Cited by 27 publications

References 45 publications

Modifying muscle mass – the endocrine perspective

Modifying muscle mass – the endocrine perspective

Nandrolone Normalizes Determinants of Muscle Mass and Fiber Type after Spinal Cord Injury

Androgens and skeletal muscle: cellular and molecular action mechanisms underlying the anabolic actions

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