Estrogen receptor-α and -β and aromatase knockout effects on lower limb muscle mass and contractile function in female mice

Estrogen receptor-α and -β and aromatase knockout effects on lower limb muscle mass and contractile function in female mice
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DOI:
10.1152/ajpendo.90696.2008
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发表时间:
2009-04-01
影响因子:
5.1
通讯作者:
Lubahn, Dennis B.
Lubahn, Dennis B.
中科院分区:
医学2区
文献类型:
--
作者:
Brown, Marybeth;Ning, Jie;Lubahn, Dennis B.

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首页--期刊主要分类--期刊细介绍--期刊题录与文摘-期刊详细文摘内容雌激素受体α、β和芳香酶基因敲除对雌性小鼠下肢肌质量和收缩功能的影响。AM J生理学内分泌代谢酶296:E854-E861,2009。据报道,雌激素(E(2))调节骨骼肌质量和收缩功能;E(2)是否通过雌激素受体-α(ER-α)或-β(ER-β)发挥作用尚不清楚。我们测定了ERα或ERβ的消除对成年雌性小鼠多块肌肉的肌肉质量和收缩功能的影响,这些肌肉具有不同的运动任务和I型和II型纤维的比例:比目鱼肌(SOL)、足底肌(Plan)、胫前肌(TA)和腓肠肌(GAST)。为了确定E2对肌肉的清除作用,我们还使用了芳香化酶(AR)基因敲除(KO)和野生型(WT)小鼠。ERα和Arko体重分别比WT高10%和20%。虽然两组的肌肉质量都有相应的增加,但只有ERα组的TA显著增加(P<0.05)。在ARKO小鼠中,肌肉质量与体重的比值显示GAST和TA的值显著降低(P<0.05)。TA和GAST的单位计算解剖横截面积(ACSA)的张力(P(O))低于WT。在组织学上,ERα、KO、Gast和TA中P(O)/ACSA的降低也受到P(O)/纤维面积显著减少的支持(P<0.05)。ARKO小鼠在GAST和TA中的Po/ACSA也低于WT。ER、BETA、KO和WT小鼠在所有指标上都具有可比性。我们的结果支持这样的假设,即E(2)对骨骼肌的作用部分是通过ERα介导的,但E(2)的作用可能是通过多种机制或受体介导的。
Brown M, Ning J, Ferreira JA, Bogener JL, Lubahn DB. Estrogen receptor-alpha and -beta and aromatase knockout effects on lower limb muscle mass and contractile function in female mice. Am J Physiol Endocrinol Metab 296: E854-E861, 2009. First published January 27, 2009; doi:10.1152/ajpendo.90696.2008.-Estrogen (E(2)) is reported to regulate skeletal muscle mass and contractile function; whether E(2) exerts its effects through estrogen receptor-alpha (ER alpha) or -beta (ER beta) is unclear. We determined the effect of ER alpha or ER beta elimination on muscle mass and contractile function in multiple muscles of the lower limb, muscles with different locomotor tasks and proportions of fiber types I and II: soleus (Sol), plantaris (Plan), tibialis anterior (TA), and gastrocnemius (Gast) in mature female mice. To determine E2 elimination effects on muscle, we also used aromatase (Ar) knockout (KO) and wild-type (WT) mice. ER alpha and ArKO body weights were similar to 10 and 20% higher than WT. Although muscle mass tended to show a commensurate increase in both groups, only the TA was significantly larger in ER alpha (P < 0.05). Ratios of muscle mass to body mass revealed significantly lower values for Gast and TA in ArKO mice (P < 0.05). Tetanic tension (P(o)) per calculated anatomical cross-sectional area (aCSA) in ER alpha KO was lower in TA and Gast than in WT. Lower P(o)/aCSA in ER alpha KO Gast and TA was also supported histologically by significantly less P(o)/fiber areas (P < 0.05). ArKO mice also had lower Po/aCSA in Gast and TA compared with WT. ER beta KO and WT mice were comparable in all measures. Our results support the hypothesis that E(2) effects on skeletal muscle are mediated in part via the ER alpha but that E(2) effects may be mediated via more than one mechanism or receptor.