肌纤维中的雄激素受体导致肌力迅速丧失，但不会导致肌肉质量下降：这对脊髓延髓肌萎缩症有影响。
Androgen receptors in muscle fibers induce rapid loss of force but not mass: implications for spinal bulbar muscular atrophy.
机构信息
Neuroscience Program, Michigan State University, 108 Giltner Hall, 293 Farm Lane, East Lansing, Michigan 48824-1101, USA.
出版信息
Muscle Nerve. 2013 Jun;47(6):823-34. doi: 10.1002/mus.23813. Epub 2013 Apr 30.
Abstract
INTRODUCTION
Testosterone (T) induces motor dysfunction in transgenic (Tg) mice that overexpress wild-type androgen receptor (AR) in skeletal muscles. Because many genes implicated in motor neuron disease are expressed in skeletal muscle, mutant proteins may act in muscle to cause dysfunction in motor neuron disease.
METHODS
We examined contractile properties of the extensor digitorum longus (EDL) and soleus (SOL) muscles in vitro after 5 and 3 days of T treatment in motor-impaired Tg female mice.
RESULTS
Both muscles showed deficits in tetanic force after 5 days of T treatment, without losses in muscle mass, protein content, or fiber number. After 3 days of T treatment, only SOL showed a deficit in tetanic force comparable to that of 5 days of treatment. In both treatments, EDL showed slowed twitch kinetics, whereas SOL showed deficits in the twitch/tetanus ratio.
CONCLUSIONS
These results suggest calcium-handling mechanisms in muscle fibers are defective in motor-impaired mice.
摘要
简介
睾丸激素（T）可导致过度表达野生型雄激素受体（AR）的转基因（Tg）小鼠出现运动功能障碍。由于许多与运动神经元疾病相关的基因在骨骼肌中表达，因此突变蛋白可能在肌肉中发挥作用，导致运动神经元疾病的功能障碍。
方法
我们在运动受损的 Tg 雌性小鼠中分别用 T 处理 5 天和 3 天后，在体外检测了伸趾长肌（EDL）和比目鱼肌（SOL）的收缩性能。
结果
5 天 T 处理后，两种肌肉的强直力均出现缺陷，而肌肉质量、蛋白含量或纤维数量均无损失。3 天 T 处理后，只有 SOL 的强直力出现缺陷，与 5 天的处理相当。在两种处理中，EDL 的慢肌动力学均减慢，而 SOL 的抽搐/强直比值出现缺陷。
结论
这些结果表明，运动受损小鼠的肌肉纤维钙处理机制存在缺陷。
相似文献
1
Androgen receptors in muscle fibers induce rapid loss of force but not mass: implications for spinal bulbar muscular atrophy.肌纤维中的雄激素受体导致肌力迅速丧失，但不会导致肌肉质量下降：这对脊髓延髓肌萎缩症有影响。
Muscle Nerve. 2013 Jun;47(6):823-34. doi: 10.1002/mus.23813. Epub 2013 Apr 30.
2
Recovery of function in a myogenic mouse model of spinal bulbar muscular atrophy.脊髓延髓肌肉萎缩症肌源性小鼠模型中功能的恢复
Neurobiol Dis. 2009 Apr;34(1):113-20. doi: 10.1016/j.nbd.2008.12.009. Epub 2008 Dec 31.
3
Pre-clinical symptoms of SBMA may not be androgen-dependent: implications from two SBMA mouse models.SBMA 的临床前症状可能与雄激素无关：来自两种 SBMA 小鼠模型的启示。
Hum Mol Genet. 2018 Jul 15;27(14):2425-2442. doi: 10.1093/hmg/ddy142.
4
Continuous testosterone administration prevents skeletal muscle atrophy and enhances resistance to fatigue in orchidectomized male mice.持续给予睾酮可预防去势雄性小鼠的骨骼肌萎缩，并增强其抗疲劳能力。
Am J Physiol Endocrinol Metab. 2006 Sep;291(3):E506-16. doi: 10.1152/ajpendo.00058.2006. Epub 2006 Apr 18.
5
Androgen Action via the Androgen Receptor in Neurons Within the Brain Positively Regulates Muscle Mass in Male Mice.雄激素通过大脑内神经元中的雄激素受体发挥作用，对雄性小鼠的肌肉质量具有正向调节作用。
Endocrinology. 2017 Oct 1;158(10):3684-3695. doi: 10.1210/en.2017-00470.
6
Acute effect of androgens on maximal force-generating capacity and electrically evoked calcium transient in mouse skeletal muscles.雄激素对小鼠骨骼肌最大力量产生能力和电诱发钙瞬变的急性影响。
Steroids. 2014 Sep;87:6-11. doi: 10.1016/j.steroids.2014.05.005. Epub 2014 May 17.
7
Contractile dysfunction in muscle may underlie androgen-dependent motor dysfunction in spinal bulbar muscular atrophy.肌肉收缩功能障碍可能是脊髓延髓性肌萎缩症中雄激素依赖性运动功能障碍的潜在原因。
J Appl Physiol (1985). 2015 Apr 1;118(7):941-52. doi: 10.1152/japplphysiol.00886.2014. Epub 2015 Feb 5.
8
A short-term statin treatment changes the contractile properties of fast-twitch skeletal muscles.短期他汀类药物治疗会改变快肌骨骼肌的收缩特性。
BMC Musculoskelet Disord. 2016 Oct 28;17(1):449. doi: 10.1186/s12891-016-1306-2.
9
Prenatal flutamide enhances survival in a myogenic mouse model of spinal bulbar muscular atrophy.产前氟他胺增强肌源性脊髓延髓肌肉萎缩症小鼠模型的存活率。
Neurodegener Dis. 2011;8(1-2):25-34. doi: 10.1159/000313682. Epub 2010 Aug 4.
10
Neurotrophic factors enhance the survival of muscle fibers in EDL, but not SOL, after neonatal nerve injury.神经营养因子可提高新生神经损伤后EDL中肌纤维的存活率，但对SOL中的肌纤维无此作用。
Am J Physiol Cell Physiol. 2002 Sep;283(3):C950-9. doi: 10.1152/ajpcell.00081.2002.
引用本文的文献
1
Glutamine supplementation accelerates functional recovery of EDL muscles after injury by modulating the expression of S100 calcium-binding proteins.谷氨酰胺补充通过调节 S100 钙结合蛋白的表达加速 EDL 肌肉损伤后的功能恢复。
Histochem Cell Biol. 2023 Aug;160(2):135-146. doi: 10.1007/s00418-023-02194-5. Epub 2023 May 14.
2
Defective excitation-contraction coupling and mitochondrial respiration precede mitochondrial Ca accumulation in spinobulbar muscular atrophy skeletal muscle.脊髓性肌萎缩症骨骼肌中线粒体钙积累之前存在兴奋-收缩偶联和线粒体呼吸缺陷。
Nat Commun. 2023 Feb 6;14(1):602. doi: 10.1038/s41467-023-36185-w.
3
Disease Affects Expression in Synaptic and Extrasynaptic Regions of Skeletal Muscle of Three SBMA Mouse Models.疾病影响三种 SBMA 小鼠模型骨骼肌突触和突触外区域的表达。
Int J Mol Sci. 2019 Mar 15;20(6):1314. doi: 10.3390/ijms20061314.
4
BGP-15 improves contractile function of regenerating soleus muscle.BGP-15 可改善再生比目鱼肌的收缩功能。
J Muscle Res Cell Motil. 2018 Apr;39(1-2):25-34. doi: 10.1007/s10974-018-9495-y. Epub 2018 Jun 11.
5
Pre-clinical symptoms of SBMA may not be androgen-dependent: implications from two SBMA mouse models.SBMA 的临床前症状可能与雄激素无关：来自两种 SBMA 小鼠模型的启示。
Hum Mol Genet. 2018 Jul 15;27(14):2425-2442. doi: 10.1093/hmg/ddy142.
6
Inhibition of retrograde transport modulates misfolded protein accumulation and clearance in motoneuron diseases.抑制逆行转运可调节运动神经元疾病中错误折叠蛋白的积累和清除。
Autophagy. 2017 Aug 3;13(8):1280-1303. doi: 10.1080/15548627.2017.1308985.
7
Decreased Peak Expiratory Flow Associated with Muscle Fiber-Type Switching in Spinal and Bulbar Muscular Atrophy.脊髓延髓肌肉萎缩症中与肌纤维类型转换相关的呼气峰值流量降低
PLoS One. 2016 Dec 22;11(12):e0168846. doi: 10.1371/journal.pone.0168846. eCollection 2016.
8
Non-Cell-Autonomous Regulation of Retrograde Motoneuronal Axonal Transport in an SBMA Mouse Model.非细胞自主调控 SBMA 小鼠模型中的逆行运动神经元轴突运输。
eNeuro. 2016 Aug 10;3(4). doi: 10.1523/ENEURO.0062-16.2016. eCollection 2016 Jul-Aug.
9
Expression of 5α- and 5β-reductase in spinal cord and muscle of birds with different courtship repertoires.5α-和5β-还原酶在具有不同求偶行为模式的鸟类脊髓和肌肉中的表达。
Front Zool. 2016 Jun 10;13:25. doi: 10.1186/s12983-016-0156-y. eCollection 2016.
10
Defects in Neuromuscular Transmission May Underlie Motor Dysfunction in Spinal and Bulbar Muscular Atrophy.神经肌肉传递缺陷可能是脊髓和延髓性肌萎缩运动功能障碍的潜在原因。
J Neurosci. 2016 May 4;36(18):5094-106. doi: 10.1523/JNEUROSCI.3485-15.2016.
本文引用的文献
1
Astrocytes in the rat medial amygdala are responsive to adult androgens.大鼠杏仁内侧核中的星形细胞对雄激素有反应。
J Comp Neurol. 2012 Aug 1;520(11):2531-44. doi: 10.1002/cne.23061.
2
Ryanodine receptor oxidation causes intracellular calcium leak and muscle weakness in aging.肌质网钙释放通道氧化导致衰老过程中的细胞内钙泄漏和肌肉无力。
Cell Metab. 2011 Aug 3;14(2):196-207. doi: 10.1016/j.cmet.2011.05.014.
3
Subcellular effects of myocyte-specific androgen receptor overexpression in mice.肌细胞特异性雄激素受体过表达对小鼠的亚细胞作用。
J Endocrinol. 2011 Jul;210(1):93-104. doi: 10.1530/JOE-11-0071. Epub 2011 May 9.
4
Native functions of the androgen receptor are essential to pathogenesis in a Drosophila model of spinobulbar muscular atrophy.雄激素受体的天然功能对肌萎缩侧索硬化的果蝇模型发病机制至关重要。
Neuron. 2010 Sep 23;67(6):936-52. doi: 10.1016/j.neuron.2010.08.034.
5
Prenatal flutamide enhances survival in a myogenic mouse model of spinal bulbar muscular atrophy.产前氟他胺增强肌源性脊髓延髓肌肉萎缩症小鼠模型的存活率。
Neurodegener Dis. 2011;8(1-2):25-34. doi: 10.1159/000313682. Epub 2010 Aug 4.
6
Myocyte androgen receptors increase metabolic rate and improve body composition by reducing fat mass.肌细胞雄激素受体通过减少脂肪量来提高代谢率并改善身体成分。
Endocrinology. 2010 Jul;151(7):3125-32. doi: 10.1210/en.2010-0018. Epub 2010 Apr 28.
7
Skeletal muscle-restricted expression of human SOD1 causes motor neuron degeneration in transgenic mice.骨骼肌特异性表达人 SOD1 导致转基因小鼠运动神经元变性。
Hum Mol Genet. 2010 Jun 1;19(11):2284-302. doi: 10.1093/hmg/ddq106. Epub 2010 Mar 10.
8
Serum creatine kinase levels in spinobulbar muscular atrophy and amyotrophic lateral sclerosis.脊髓延髓肌肉萎缩症和肌萎缩侧索硬化症患者的血清肌酸激酶水平
Muscle Nerve. 2009 Jul;40(1):126-9. doi: 10.1002/mus.21310.
9
Muscle mitochondrial uncoupling dismantles neuromuscular junction and triggers distal degeneration of motor neurons.肌肉线粒体解偶联破坏神经肌肉接头并引发运动神经元的远端变性。
PLoS One. 2009;4(4):e5390. doi: 10.1371/journal.pone.0005390. Epub 2009 Apr 30.
10
Phase 2 trial of leuprorelin in patients with spinal and bulbar muscular atrophy.亮丙瑞林治疗脊髓延髓性肌萎缩症患者的2期试验。
Ann Neurol. 2009 Feb;65(2):140-50. doi: 10.1002/ana.21540.
Zotero 插件