Estradiol treatment, physical activity, and muscle function in ovarian-senescent mice.

Estradiol treatment, physical activity, and muscle function in ovarian-senescent mice.
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DOI:
10.1016/j.exger.2011.04.006
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发表时间:
2011-08
影响因子:
3.9
通讯作者:
Lowe, Dawn A.
Lowe, Dawn A.
中科院分区:
医学2区
文献类型:
--
作者:
Greising, Sarah M.;Carey, Ryan S.;Blackford, Jennifer E.;Dalton, Laurin E.;Kosir, Allison M.;Lowe, Dawn A.

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雌二醇(E_2)对去卵巢的年轻成年小鼠的治疗增加了体力活动,并逆转了对骨骼肌的有害影响。在这里,我们测试了E2治疗改善老年卵巢衰老小鼠肌肉功能和体力活动的假设。血浆雌二醇水平和阴道细胞学检查证实20个月大的C57BL/6小鼠卵巢衰老。然后,小鼠被随机分为活动组,无论是否有机会使用转轮,并进一步分为接受E2或安慰剂的组。安慰剂组小鼠的轮子跑得比雌二醇组小鼠多(P=0.03),在笼子活动方面,两组之间没有差异,如活动时间和行走距离(P≥0.55)。来自轮子的老年小鼠的比目鱼肌通过变得更大和更强壮来适应,与E2状态无关(P≤0.02)。E2组小鼠比目鱼肌抗疲劳能力强(P=0.0 2),但对最大等长强直力无影响(P≥0.79)。由于E2治疗没有像预期的那样改善老年卵巢衰老小鼠的体力活动或整体肌肉功能,因此启动了第二项研究,以检验E2治疗因接触化学物质4-乙烯基环己烯二环氧化物(VCD)而导致卵巢过早衰老的年轻成年小鼠。4月龄C57BL/6雌性小鼠分别给予油(对照组)和VCD灌胃。阴道细胞学检查证实,所有用VCD治疗的小鼠在开始给药63天后卵巢衰老,然后VCD小鼠的一部分接受E2(VCD+E2)。对照组、Vcd组和Vcd+E2组小鼠的车轮运行距离无显著差异(P>≥)。VCD+E2组比目鱼肌的向心力、等长力和离心力比VCD组小鼠大(P<0.04),这表明雌激素对肌肉功能有好处。总体而言,卵巢老化的老年和年轻小鼠在体力活动和肌肉功能方面对E2治疗的反应低于先前对年轻的卵巢切除小鼠的反应。这些结果表明,残留的、卵泡耗尽的卵巢组织的某些成分可能会影响小鼠的体力活动,或者衰老会降低骨骼肌和相关组织对E2治疗的反应性。
Estradiol (E2) treatment in young adult, ovariectomized mice increases physical activity and reverses deleterious effects on skeletal muscle. Here we test the hypothesis that E2 treatment improves muscle function and physical activity in aged, ovarian-senescent mice. Plasma E2 levels and vaginal cytology confirmed ovarian senescence in 20-month-old C57BL/6 mice. Mice were then randomly divided into activity groups, having access to a running wheel or not, and further into those receiving E2 or placebo. Placebo-treated mice wheel ran more than E2-treated mice (P=0.03), with no difference between treatment groups in cage activities such as time spent being active and ambulation distance (P≥0.55). Soleus muscles from aged mice that wheel ran adapted by getting larger and stronger, irrespective of E2 status (P≤0.02). Soleus muscle fatigue resistance was greater in mice treated with E2 (P=0.02), but maximal isometric tetanic force was not affected (P≥0.79). Because E2 treatment did not improve physical activity or overall muscle function in the aged, ovarian-senescent mice as predicted, a second study was initiated to examine E2 treatment of young adult mice prematurely ovarian senescent from exposure to the chemical, 4-vinylcyclohexene diepoxide (VCD). 4-month-old C57BL/6 female mice were dosed with oil (control) or VCD. Vaginal cytology confirmed ovarian senescence in all mice treated with VCD 63 days after the onset of dosing, and then a subset of the VCD mice received E2 (VCD+E2). Wheel running distance did not differ among control, VCD, and VCD+E2 mice (P≥0.34). Soleus muscle concentric, isometric, and eccentric in vitro forces were greater in VCD+E2 than VCD mice (P<0.04), indicating beneficial estrogenic effects on muscle function. In general, aged and young mice with senescent ovaries were less responsive to E2 treatment, in terms of physical activities and muscle function, than what has previously been shown for young, ovariectomized mice. These results bring forth the possibility that some component of the residual, follicle-depleted ovarian tissue influences physical activity in mice or that aging diminishes the responsiveness of skeletal muscle and related tissues to E2 treatment.
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