دورية أكاديمية
Deletion of estrogen receptor α in skeletal muscle results in impaired contractility in female mice.
| العنوان: | Deletion of estrogen receptor α in skeletal muscle results in impaired contractility in female mice. |
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| المؤلفون: | Collins BC; Divisions of Rehabilitation Science and Physical Therapy, Department of Rehabilitation Medicine, Medical School, University of Minnesota , Minneapolis, Minnesota., Mader TL; Divisions of Rehabilitation Science and Physical Therapy, Department of Rehabilitation Medicine, Medical School, University of Minnesota , Minneapolis, Minnesota., Cabelka CA; Divisions of Rehabilitation Science and Physical Therapy, Department of Rehabilitation Medicine, Medical School, University of Minnesota , Minneapolis, Minnesota., Iñigo MR; East Carolina Diabetes and Obesity Institute, Department of Physiology, Brody School of Medicine, East Carolina University , Greenville, North Carolina., Spangenburg EE; East Carolina Diabetes and Obesity Institute, Department of Physiology, Brody School of Medicine, East Carolina University , Greenville, North Carolina., Lowe DA; Divisions of Rehabilitation Science and Physical Therapy, Department of Rehabilitation Medicine, Medical School, University of Minnesota , Minneapolis, Minnesota. |
| المصدر: | Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol (1985)] 2018 Apr 01; Vol. 124 (4), pp. 980-992. Date of Electronic Publication: 2018 Jan 18. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 8502536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1601 (Electronic) Linking ISSN: 01617567 NLM ISO Abbreviation: J Appl Physiol (1985) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, MD : American Physiological Society, c1985- |
| مواضيع طبية MeSH: | Muscle Contraction* , Muscle Strength*, Estradiol/*metabolism , Estrogen Receptor alpha/*metabolism , Muscle, Skeletal/*metabolism, Animals ; Female ; Mice, Knockout ; Motor Activity |
| مستخلص: | Estradiol deficiency in females can result in skeletal muscle strength loss, and treatment with estradiol mitigates the loss. There are three primary estrogen receptors (ERs), and estradiol elicits effects through these receptors in various tissues. Ubiquitous ERα-knockout mice exhibit numerous biological disorders, but little is known regarding the specific role of ERα in skeletal muscle contractile function. The purpose of this study was to determine the impact of skeletal muscle-specific ERα deletion on contractile function, hypothesizing that ERα is a main receptor through which estradiol affects muscle strength in females. Deletion of ERα specifically in skeletal muscle (skmERαKO) did not affect body mass compared with wild-type littermates (skmERαWT) until 26 wk of age, at which time body mass of skmERαKO mice began to increase disproportionally. Overall, skmERαKO mice had low strength demonstrated in multiple muscles and by several contractile parameters. Isolated extensor digitorum longus muscles from skmERαKO mice produced 16% less eccentric and 16-26% less submaximal and maximal isometric force, and isolated soleus muscles were more fatigable, with impaired force recovery relative to skmERαWT mice. In vivo maximal torque productions by plantarflexors and dorsiflexors were 16% and 12% lower in skmERαKO than skmERαWT mice, and skmERαKO muscles had low phosphorylation of myosin regulatory light chain. Plantarflexors also generated 21-32% less power, submaximal isometric and peak concentric torques. Data support the hypothesis that ablation of ERα in skeletal muscle results in muscle weakness, suggesting that the beneficial effects of estradiol on muscle strength are receptor mediated through ERα. NEW & NOTEWORTHY We comprehensively measured in vitro and in vivo skeletal muscle contractility in female estrogen receptor α (ERα) skeletal muscle-specific knockout mice and report that force generation is impaired across multiple parameters. These results support the hypothesis that a primary mechanism through which estradiol elicits its effects on strength is mediated by ERα. Evidence is presented that estradiol signaling through ERα appears to modulate force at the molecular level via posttranslational modifications of myosin regulatory light chain. |
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| معلومات مُعتمدة: | R01 AG031743 United States AG NIA NIH HHS; T32 AG029796 United States AG NIA NIH HHS; T32 AR007612 United States AR NIAMS NIH HHS |
| فهرسة مساهمة: | Keywords: estradiol; hormone receptor; muscle physiology; power; strength |
| المشرفين على المادة: | 0 (Estrogen Receptor alpha) 4TI98Z838E (Estradiol) |
| تواريخ الأحداث: | Date Created: 20180119 Date Completed: 20191107 Latest Revision: 20220120 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC5972463 |
| DOI: | 10.1152/japplphysiol.00864.2017 |
| PMID: | 29345963 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1601 |
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| DOI: | 10.1152/japplphysiol.00864.2017 |