Voluntary running, skeletal muscle gene expression, and signaling inversely regulated by orchidectomy and testosterone replacement
Voluntary running, skeletal muscle gene expression, and signaling inversely regulated by orchidectomy and testosterone replacement
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DOI：
10.1152/ajpendo.00402.2010
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发表时间：
2011-02-01
影响因子：
5.1
通讯作者：
Glass, David J.
中科院分区：
文献类型：
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作者：
Ibebunjo, Chikwendu;Eash, John K.;Glass, David J.
Ibebunjo C，Eash JK，Li C，Ma Q，Glass DJ.自愿运行，骨骼肌基因表达，并通过睾丸切除术和睾酮替代反向调节信号。Am J Physiol Endocrinol Metab 300：E327-E340，2011。首次发表于2010年11月2日; doi：10.1152/ajpendo.00402.2010.-骨骼肌大小和强度的下降，通常与慢性消耗性疾病、长期或高剂量糖皮质激素治疗以及哺乳动物的自然衰老过程有关，通常与体力活动和睾酮水平降低有关。然而，目前尚不清楚睾酮和活动的下降是否存在因果关系。使用小鼠模型，我们发现，去除内源性睾酮的睾丸切除术的结果在自愿轮运行几乎完全停止，但只有一个小的肌肉质量下降。替吉奥使跑步行为和肌肉质量恢复到正常水平。睾丸切除术还抑制了IGF-I/Akt通路，激活了萎缩诱导E3连接酶MuRF 1和MAFBx，并抑制了几种能量代谢途径，所有这些作用都被睾酮替代逆转。这项研究还描绘了一个独特的，以前未识别的基因组，这是由睾丸切除术和睾酮治疗负调控。这些数据证明了睾酮对小鼠自愿轮跑的速度和耐力的必要性，并表明了雄激素缺乏的人类活动下降的潜在机制。
Ibebunjo C, Eash JK, Li C, Ma Q, Glass DJ. Voluntary running, skeletal muscle gene expression, and signaling inversely regulated by orchidectomy and testosterone replacement. Am J Physiol Endocrinol Metab 300: E327-E340, 2011. First published November 2, 2010; doi: 10.1152/ajpendo.00402.2010.-Declines in skeletal muscle size and strength, often seen with chronic wasting diseases, prolonged or high-dose glucocorticoid therapy, and the natural aging process in mammals, are usually associated with reduced physical activity and testosterone levels. However, it is not clear whether the decline in testosterone and activity are causally related. Using a mouse model, we found that removal of endogenous testosterone by orchidectomy results in an almost complete cessation in voluntary wheel running but only a small decline in muscle mass. Testosterone replacement restored running behavior and muscle mass to normal levels. Orchidectomy also suppressed the IGF-I/Akt pathway, activated the atrophyinducing E3 ligases MuRF1 and MAFBx, and suppressed several energy metabolism pathways, and all of these effects were reversed by testosterone replacement. The study also delineated a distinct, previously unidentified set of genes that is inversely regulated by orchidectomy and testosterone treatment. These data demonstrate the necessity of testosterone for both speed and endurance of voluntary wheel running in mice and suggest a potential mechanism for declined activity in humans where androgens are deficient.