Generation and analysis of an androgen-responsive myoblast cell line indicates that androgens regulate myotube protein accretion

Chen, Y; Lee, Nicole K. L.; Zajac, Jeffrey D; MacLean, Helen E.

doi:10.1007/bf03346441

Cited by 18 publications

(16 citation statements)

References 35 publications

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“…Different studies have suggested that androgens act on satellite cells or myoblasts to increase the number of myonuclei (Mulvaney et al 1988, Joubert et al 1994, Joubert & Tobin 1995 or act on myofibers to increase protein content (Sheffield-Moore et al 1999, Ferrando et al 2002, Chen et al 2008, Ophoff et al 2009b. However, despite the fact that the AR is deleted by ≥93% in hind-limb muscles of both mAR ΔZF2 lines in our study, muscle mass is virtually normal with only relative muscle mass decreased in α-actin mAR ΔZF2 TA and soleus, but all other hind-limb muscles not different to AR lox controls.…”

Section: Discussionmentioning

confidence: 99%

“…Adult skeletal muscle fibers are terminally differentiated, and muscle repair and hypertrophy can occur either through an increase in the number of myonuclei, via activation of satellite cells (muscle stem cells) to proliferate as myoblasts, differentiate into myotubes and fuse with myofibers, or via an increase in protein content of postproliferative myofibers. While some studies have shown that androgens increase myoblast proliferation rate and/or delay differentiation (Powers & Florini 1975, Doumit et al 1996, Sinha-Hikim et al 2006, Diel et al 2008, others suggest the predominant actions are on protein accretion in myofibers (Ferrando et al 1998, Chen et al 2008. Maximal hypertrophic response to muscle overloading requires myofiber AR, but also involves other target cells (Ferry et al 2014).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Muscle-specific androgen receptor deletion shows limited actions in myoblasts but not in myofibers in different muscles in vivo

Rana¹,

Chiu²,

Russell³

et al. 2016

Journal of Molecular Endocrinology

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The aim of this study was to investigate the direct muscle cell-mediated actions of androgens by comparing two different mouse lines. The cre-loxP system was used to delete the DNA-binding activity of the androgen receptor (AR) in mature myofibers (MCK mAR ΔZF2 ) in one model and the DNA-binding activity of the AR in both proliferating myoblasts and myofibers (α-actin mAR ΔZF2 ) in another model. We found that hind-limb muscle mass was normal in MCK mAR ΔZF2 mice and that relative mass of only some hind-limb muscles was reduced in α-actin mAR ΔZF2 mice. This suggests that myoblasts and myofibers are not the major cellular targets mediating the anabolic actions of androgens on male muscle during growth and development. Levator ani muscle mass was decreased in both mouse lines, demonstrating that there is a myofiber-specific effect in this unique androgen-dependent muscle. We found that the pattern of expression of genes including c-myc, Fzd4 and Igf2 is associated with androgen-dependent changes in muscle mass; therefore, these genes are likely to be mediators of anabolic actions of androgens. Further research is required to identify the major targets of androgen actions in muscle, which are likely to include indirect actions via other tissues.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Muscle-specific androgen receptor deletion shows limited actions in myoblasts but not in myofibers in different muscles in vivo

Rana¹,

Chiu²,

Russell³

et al. 2016

Journal of Molecular Endocrinology

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“…C2C12 cells stably transfected with truncated ODC (pCMV-ODCT; kindly provided by Lisa Shantz, Department of Cellular and Molecular Physiology, Penn State Milton S. Hershey Medical Center) were generated as previously described (21). The ODC protein is truncated by 37 amino acids by insertion of a termination codon at position 426, which results in ODC protein with a extended half-life (41).…”

Section: Micementioning

confidence: 99%

“…To determine if ODC regulates proliferation, proliferating C2C12 myoblasts, which we previously used as a model of myoblast proliferation (21), were treated with difluoromethylornithine (DFMO; Chem-Impex), an irreversible and specific inhibitor of ODC. Myoblasts were seeded in proliferation medium for 1 h and then treated for 24, 48, or 72 h (n ϭ 4 -6/cell line), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to measure myoblast number at each time point.…”

Section: Micementioning

confidence: 99%

Ornithine decarboxylase is upregulated by the androgen receptor in skeletal muscle and regulates myoblast proliferation

Lee

Skinner

Zajac

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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The aim of this study is to determine if the Odc1 gene, which encodes ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, is directly regulated by the androgen receptor (AR) in skeletal muscle myoblasts and if Odc1 regulates myoblast proliferation and differentiation. We previously showed that expression of Odc1 is decreased in muscle from AR knockout male mice. In this study, we show in vivo that Odc1 expression is also decreased >60% in muscle from male muscle-specific AR knockout mice. In normal muscle homeostasis, Odc1 expression is regulated by age and sex, reflecting testosterone levels, as muscle of adult male mice expresses high levels of Odc1 compared with age-matched females and younger males. In vitro, expression of Odc1 is 10- and 1.5-fold higher in proliferating mouse C(2)C(12) and human skeletal muscle myoblasts, respectively, than in differentiated myotubes. Dihydrotestosterone increases Odc1 levels 2.7- and 1.6-fold in skeletal muscle cell myoblasts after 12 and 24 h of treatment, respectively. Inhibition of ODC activity in C(2)C(12) myoblasts by α-difluoromethylornithine decreases myoblast number by 40% and 66% following 48 and 72 h of treatment, respectively. In contrast, overexpression of Odc1 in C(2)C(12) myoblasts results in a 27% increase in cell number vs. control when cells are grown under differentiation conditions for 96 h. This prolonged proliferation is associated with delayed differentiation, with reduced expression of the differentiation markers myogenin and Myf6 in Odc1-overexpressing cells. In conclusion, androgens act via the AR to upregulate Odc1 in skeletal muscle myoblasts, and Odc1 promotes myoblast proliferation and delays differentiation.

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“…In adapting muscle, satellite cells are activated, proliferate and subsequently fuse with muscle fibers [82]. Androgens regulate satellite cell activity through the androgen receptor but the fastest nongenomic effect of anabolic action has not been shown (reviewed in [83]). …”

Section: Satellite Cells and Anabolic Effectmentioning

confidence: 99%

Phytoecdysteroids and Anabolic-Androgenic Steroids - Structure and Effects on Humans

Báthori¹,

Tóth²,

Hunyadi³

et al. 2008

CMC

172

168

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Phytoecdysteroids are structural analogs of the insect molting hormone ecdysone. Plants comprise rich sources of ecdysteroids in high concentration and with broad structural diversity. Ecdysteroids have a number of proven beneficial effects on mammals but the hormonal effects of ecdysteroids have been proven only in arthropods. Their structures are somewhat similar to those of the vertebrate steroid hormones but there are several structural differences between the two steroid groups. Despite of these essential structural differences, ecdysteroids exert numerous effects in vertebrates that are similar to those of vertebrate hormonal steroids, and they may serve as effective anabolic, hepatoprotective, immunoprotective, antioxidant and hypoglycemic agents.Ecdysteroids do not bind to the cytosolic steroid receptors, instead, they are likely to influence signal transduction pathways, like the anabolic steroids, possibly via membrane bound receptors.The application of phytoecdysteroids is a promising alternative to the use of anabolic-androgenic steroids because of the apparent lack of adverse effects. The prospective use of phytoecdysteroids may extend to treatments of pathological conditions where anabolic steroids are routinely applied. One of the most cited aspects of phytoecdysteroid application (on the Internet) is the increase of muscle size. However in this field too stringent research is needed as an adequate cytological explanation is not yet available for the anabolic. This paper reports on the most important structural differences between androgenic hormones, their synthetic analogs and ecdysteroids. The anabolic/hormonal effects and the possible mechanisms of action of these compounds are also discussed as concerns the skeletal muscle.

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Generation and analysis of an androgen-responsive myoblast cell line indicates that androgens regulate myotube protein accretion

Cited by 18 publications

References 35 publications

Muscle-specific androgen receptor deletion shows limited actions in myoblasts but not in myofibers in different muscles in vivo

Muscle-specific androgen receptor deletion shows limited actions in myoblasts but not in myofibers in different muscles in vivo

Ornithine decarboxylase is upregulated by the androgen receptor in skeletal muscle and regulates myoblast proliferation

Phytoecdysteroids and Anabolic-Androgenic Steroids - Structure and Effects on Humans

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