Sitnick Mitchell, Foley Andrea M, Brown Marybeth, Spangenburg Espen E
Molecular, Cellular, and Integrative Physiology Graduate Group, University of California, Davis, One Shields Ave., Davis, California 95616, USA.
J Appl Physiol (1985). 2006 Jan;100(1):286-93. doi: 10.1152/japplphysiol.00869.2005. Epub 2005 Sep 8.
The recovery of atrophied muscle mass in animals is thought to be dependent on a number of factors including hormones, cytokines, and/or growth factor expression. The Akt/mammalian target of rapamycin (mTOR) signaling pathway is believed to be activated by these various factors, resulting in skeletal muscle growth through the initiation of protein synthesis. It was hypothesized that surgical removal of the ovaries (Ovx) may alter activation of the Akt/mTOR signaling pathway, a mechanism necessary for muscle regrowth. To test this, 36 Sprague-Dawley rats underwent Ovx or sham surgeries. A portion of the animals were then subjected to hindlimb unloading (HLU) for 28 days. After HLU, one group of Sham and Ovx rats underwent a 14-day recovery period in which the animals were allowed free cage ambulation. The HLU animals demonstrated approximately 21-27% reduction in medial gastrocnemius muscle mass irrespective of whether the ovaries were intact or not. The Sham animals that were reloaded recovered their atrophied muscle mass; however, the Ovx group failed to recover any of the atrophied muscle mass with reloading. The failure to recover muscle mass in the Ovx group was associated with reduced phosphorylation levels of both Akt and p70s6k, whereas in the Sham recovery animals no reductions were found in Akt phosphorylation and significant increases in p70s6k activation were detected. Finally, no differences were detected in mTOR phosphorylation in any of Sham or Ovx groups. These results suggest that ovariectomy surgeries could be detrimental to the recovery of atrophied muscle mass.
动物萎缩肌肉质量的恢复被认为取决于多种因素，包括激素、细胞因子和/或生长因子的表达。Akt/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路被认为会被这些不同因素激活，从而通过启动蛋白质合成导致骨骼肌生长。据推测，手术切除卵巢（Ovx）可能会改变Akt/mTOR信号通路的激活，而该通路是肌肉再生所必需的机制。为了验证这一点，36只Sprague-Dawley大鼠接受了卵巢切除或假手术。然后，一部分动物进行了28天的后肢卸载（HLU）。HLU后，一组假手术和卵巢切除大鼠经历了14天的恢复期，在此期间动物可自由在笼内活动。无论卵巢是否完整，HLU动物的内侧腓肠肌质量均减少了约21%-27%。重新加载的假手术动物恢复了萎缩的肌肉质量；然而，卵巢切除组在重新加载后未能恢复任何萎缩的肌肉质量。卵巢切除组未能恢复肌肉质量与Akt和p70s6k的磷酸化水平降低有关，而在假手术恢复动物中，未发现Akt磷酸化水平降低，且检测到p70s6k激活显著增加。最后，在任何假手术或卵巢切除组中均未检测到mTOR磷酸化的差异。这些结果表明，卵巢切除手术可能不利于萎缩肌肉质量的恢复。
