Effects of ovarian hormones and estrogen receptor α on physical activity and skeletal muscle fatigue in female mice

Christine A. Cabelka, Cory W Baumann, Brittany C. Collins, Nardina Nash, Gengyun Le, Angus Lindsay, Espen E. Spangenburg, Dawn A Lowe

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 2 ) specific. Thus, the overall purpose of this study was to investigate the effects of the ovarian hormones, E 2 and progesterone (P4), and skeletal muscle ERα (skmERα) on physical activity and skeletal muscle contractility in female mice. Methods: 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 2 , OVX + P4, OVX + E 2 + 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. Results: Study 1: OVX + E 2 + 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 2 + P4 group maintained greater submaximal force than those of other groups (p = 0.023). Immediately after the fatiguing contractions, OVX + E 2 + P4 muscles had greater maximal force production than the OVX + E 2 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). Conclusions: Combined treatment of E 2 + P4 in OVX mice restored physical activity, predominantly driven by E 2 , 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.

Original languageEnglish (US)
Pages (from-to)155-164
Number of pages10
JournalExperimental Gerontology
Volume115
DOIs
StatePublished - Jan 1 2019

Fingerprint

Muscle Fatigue
Estrogen Receptors
Muscle
Skeletal Muscle
Fatigue of materials
Hormones
Knockout Mice
Running
Wheels
Muscles
Estradiol
Torque
Muscle Strength
Ovariectomy
Menopause

Keywords

  • ERα
  • Estradiol
  • Fatigue
  • Progesterone
  • Skeletal muscle
  • Wheel running

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

Cite this

Effects of ovarian hormones and estrogen receptor α on physical activity and skeletal muscle fatigue in female mice. / Cabelka, Christine A.; Baumann, Cory W; Collins, Brittany C.; Nash, Nardina; Le, Gengyun; Lindsay, Angus; Spangenburg, Espen E.; Lowe, Dawn A.

In: Experimental Gerontology, Vol. 115, 01.01.2019, p. 155-164.

Research output: Contribution to journalArticle

Cabelka, Christine A. ; Baumann, Cory W ; Collins, Brittany C. ; Nash, Nardina ; Le, Gengyun ; Lindsay, Angus ; Spangenburg, Espen E. ; Lowe, Dawn A. / Effects of ovarian hormones and estrogen receptor α on physical activity and skeletal muscle fatigue in female mice. In: Experimental Gerontology. 2019 ; Vol. 115. pp. 155-164.
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abstract = "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 2 ) specific. Thus, the overall purpose of this study was to investigate the effects of the ovarian hormones, E 2 and progesterone (P4), and skeletal muscle ERα (skmERα) on physical activity and skeletal muscle contractility in female mice. Methods: 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 2 , OVX + P4, OVX + E 2 + 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. Results: Study 1: OVX + E 2 + 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 2 + P4 group maintained greater submaximal force than those of other groups (p = 0.023). Immediately after the fatiguing contractions, OVX + E 2 + P4 muscles had greater maximal force production than the OVX + E 2 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). Conclusions: Combined treatment of E 2 + P4 in OVX mice restored physical activity, predominantly driven by E 2 , 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.",
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T1 - Effects of ovarian hormones and estrogen receptor α on physical activity and skeletal muscle fatigue in female mice

AU - Cabelka, Christine A.

AU - Baumann, Cory W

AU - Collins, Brittany C.

AU - Nash, Nardina

AU - Le, Gengyun

AU - Lindsay, Angus

AU - Spangenburg, Espen E.

AU - Lowe, Dawn A

PY - 2019/1/1

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N2 - 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 2 ) specific. Thus, the overall purpose of this study was to investigate the effects of the ovarian hormones, E 2 and progesterone (P4), and skeletal muscle ERα (skmERα) on physical activity and skeletal muscle contractility in female mice. Methods: 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 2 , OVX + P4, OVX + E 2 + 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. Results: Study 1: OVX + E 2 + 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 2 + P4 group maintained greater submaximal force than those of other groups (p = 0.023). Immediately after the fatiguing contractions, OVX + E 2 + P4 muscles had greater maximal force production than the OVX + E 2 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). Conclusions: Combined treatment of E 2 + P4 in OVX mice restored physical activity, predominantly driven by E 2 , 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.

AB - 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 2 ) specific. Thus, the overall purpose of this study was to investigate the effects of the ovarian hormones, E 2 and progesterone (P4), and skeletal muscle ERα (skmERα) on physical activity and skeletal muscle contractility in female mice. Methods: 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 2 , OVX + P4, OVX + E 2 + 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. Results: Study 1: OVX + E 2 + 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 2 + P4 group maintained greater submaximal force than those of other groups (p = 0.023). Immediately after the fatiguing contractions, OVX + E 2 + P4 muscles had greater maximal force production than the OVX + E 2 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). Conclusions: Combined treatment of E 2 + P4 in OVX mice restored physical activity, predominantly driven by E 2 , 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.

KW - ERα

KW - Estradiol

KW - Fatigue

KW - Progesterone

KW - Skeletal muscle

KW - Wheel running

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