Divisions of Rehabilitation Science and Physical Therapy, Department of Rehabilitation Medicine, Medical School, University of Minnesota, Minneapolis, Minnesota; MMC 388, 420 Delaware St SE, Minneapolis, MN 55455, USA.
Divisions of Rehabilitation Science and Physical Therapy, Department of Rehabilitation Medicine, Medical School, University of Minnesota, Minneapolis, Minnesota; MMC 388, 420 Delaware St SE, Minneapolis, MN 55455, USA; Department of Biochemistry Molecular Biology and Biophysics, University of Minnesota, 420 Washington Ave SE, Minneapolis, MN 55455, USA.
Exp Gerontol. 2019 Jan;115:155-164. doi: 10.1016/j.exger.2018.11.003. Epub 2018 Nov 8.
Menopause is associated with declines in physical activity and skeletal muscle strength. Physical activity is also reduced in rodents after ovariectomy (OVX) and whole-body estrogen receptor α (ERα) knockout. However, it is unclear if the effects are estradiol (E) specific. Thus, the overall purpose of this study was to investigate the effects of the ovarian hormones, E and progesterone (P4), and skeletal muscle ERα (skmERα) on physical activity and skeletal muscle contractility in female mice.
Study 1: Forty female C57Bl/6J mice were given free access to running wheels for 2 weeks to assess baseline running and randomized into 4 treatment groups: OVX, OVX + E, OVX + P4, OVX + E + P4. All mice underwent OVX, returned to wheels for 2 weeks, received hormone pellet implants and returned to running wheels for 6 weeks, after which soleus muscle contractility testing was completed. Study 2: Thirty-two skeletal muscle specific ERα knock-out (skmERαKO) mice and wildtype (WT) littermates were randomized into 4 groups: skmERαKO-Run, skmERαWT-Run, skmERαKO-Sed, and skmERαWT-Sed. Run mice were given free access to wheels for 20 wk and sedentary (Sed) mice maintained normal cage activities. At the end point, muscle contractility was tested.
Study 1: OVX + E + P4 group ran greater distances than both the OVX and OVX + P4 groups (p ≤ 0.009). After fatiguing contractions, soleus muscles of the OVX + E + P4 group maintained greater submaximal force than those of other groups (p = 0.023). Immediately after the fatiguing contractions, OVX + E + P4 muscles had greater maximal force production than the OVX + E group (p = 0.027). Study 2: There were no differences in running distance between skmERαWT and skmERαKO mice (p = 0.240). Soleus muscles of skmERαKO mice were more fatigable (p < 0.001) and did not recover force as well as skmERαWT mice (p < 0.001). In vivo isometric, concentric and eccentric torque was decreased in skmERαKO mice compared to skmERαWT mice (p ≤ 0.029).
Combined treatment of E + P4 in OVX mice restored physical activity, predominantly driven by E, and protected soleus muscles against fatigue. Muscle of skmERαKO mice was weak regardless of physical activity. Although 20 wk of wheel running partially prevented force loss during fatigue in skmERαKO mice, force production during recovery remained low, indicating that estradiol functions through ERα in skeletal muscle.
探讨卵巢激素雌二醇（E）和孕激素（P4）以及骨骼肌雌激素受体 α（skmERα）对雌性小鼠体力活动和骨骼肌收缩力的影响。
研究 1：40 只 C57Bl/6J 雌性小鼠可自由使用跑步轮 2 周，以评估基线跑步情况，并随机分为 4 个治疗组：OVX、OVX+E、OVX+P4 和 OVX+E+P4。所有小鼠接受 OVX，返回跑步轮 2 周，接受激素丸植入物，返回跑步轮 6 周，然后完成比目鱼肌收缩力测试。研究 2：32 只骨骼肌特异性 ERα 敲除（skmERαKO）小鼠和野生型（WT）同窝小鼠随机分为 4 组：skmERαKO-Run、skmERαWT-Run、skmERαKO-Sed 和 skmERαWT-Sed。跑步组可自由使用跑步轮 20 周，而久坐（Sed）组保持正常笼内活动。在终点时，测试肌肉收缩力。
研究 1：OVX+E+P4 组的跑步距离大于 OVX 和 OVX+P4 组（p≤0.009）。在疲劳收缩后，OVX+E+P4 组的比目鱼肌保持的次最大力大于其他组（p=0.023）。在疲劳收缩后立即，OVX+E+P4 肌肉的最大力产生大于 OVX+E 组（p=0.027）。研究 2：skmERαWT 和 skmERαKO 小鼠的跑步距离无差异（p=0.240）。skmERαKO 小鼠的比目鱼肌更易疲劳（p<0.001），恢复力不如 skmERαWT 小鼠（p<0.001）。与 skmERαWT 小鼠相比，skmERαKO 小鼠的体内等长、向心和离心扭矩降低（p≤0.029）。
OVX 小鼠中 E+P4 的联合治疗恢复了体力活动，主要由 E 驱动，并保护比目鱼肌免受疲劳。skmERαKO 小鼠的肌肉即使在进行体力活动时也很弱。尽管 20 周的轮跑部分预防了 skmERαKO 小鼠在疲劳过程中的力损失，但恢复期间的力产生仍然较低，表明雌二醇通过骨骼肌中的 ERα 发挥作用。
