Oestradiol affects skeletal muscle mass, strength and satellite cells following repeated injuries

Larson, Alexie A.; Baumann, Cory W.; Kyba, Michael; Lowe, Dawn A.

doi:10.1113/ep088827

Cited by 20 publications

(13 citation statements)

References 43 publications

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“…However, they found no difference in strength loss between E2-treated and untreated 20 month-old female mdx mice after 9 ECC indicating that E2 is not protective to muscle when challenged simultaneously by aging and dystrophin deficiency [ 49 ]. Indeed, recovery of strength was impaired in OVX mdx mice relative to sham mdx mice in the current study, consistent with our previous work in wild-type (WT) mice demonstrating that OVX mice recovered ~20% less isometric torque 1–3 weeks after injury compared to sham mice or E2-treated OVX mice [ 34 , 35 , 50 , 51 ].…”

Section: Discussionsupporting

confidence: 92%

“…To assess fatigability and recovery of strength after fatigue, the diaphragm muscle strip performed 120 submaximal isometric contractions (40 Hz for 330 ms with 0.5 ms pulses) every s over a 2 min period. A fatigue index (FI) [ 51 ] assessing fatigue resistance was calculated as the ratio of the final force (FF) measured after 2 min of 120 submaximal contractions to the initial force (IF): . Fatigue recovery was assessed by determining P o at 15 s (0 min), 2 min, 4 min, and 6 min after the fatigue protocol.…”

Section: Methods and Experimental Designmentioning

confidence: 99%

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Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice

et al. 2021

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Female carriers of Duchenne muscular dystrophy (DMD) presenting with DMD symptomology similar to males with DMD, such as skeletal muscle weakness and cardiomyopathy, are termed manifesting carriers. There is phenotypic variability among manifesting carriers including the age of onset, which can range from the first to fourth decade of life. In females, estrogen levels typically begin to decline during the fourth decade of life and estrogen deficiency contributes to loss of muscle strength and recovery of strength following injury. Thus, we questioned whether the decline of estrogen impacts the development of DMD symptoms in females. To address this question, we studied 6–8 month-old homozygous mdx female mice randomly assigned to a sham or ovariectomy (OVX) surgical group. In vivo whole-body plethysmography assessed ventilatory function and diaphragm muscle strength was measured in vitro before and after fatigue. Anterior crural muscles were analyzed in vivo for contractile function, fatigue, and in response to eccentric contraction (ECC)-induced injury. For the latter, 50 maximal ECCs were performed by the anterior crural muscles to induce injury. Body mass, uterine mass, hypoxia-hypercapnia ventilatory response, and fatigue index were analyzed by a pooled unpaired t-test. A two-way ANOVA was used to analyze ventilatory measurements. Fatigue and ECC-injury recovery experiments were analyzed by a two-way repeated-measures ANOVA. Results show no differences between sham and OVX mdx mice in ventilatory function, strength, or recovery of strength after fatigue in the diaphragm muscle or anterior crural muscles (p ≥ 0.078). However, OVX mice had significantly greater eccentric torque loss and blunted recovery of strength after ECC-induced injury compared to sham mice (p ≤ 0.019). Although the results show that loss of estrogen has minimal impact on skeletal muscle contractile function in female mdx mice, a key finding suggests that estrogen is important in muscle recovery in female mdx mice after injury.

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Section: Discussionsupporting

confidence: 92%

Section: Methods and Experimental Designmentioning

confidence: 99%

Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice

et al. 2021

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Section: Introductionmentioning

confidence: 88%

“…Our recent findings show that the size of the satellite cell pool is reduced in ovarian hormone-deficient female mice and humans under normal homeostatic conditions ( 60 , 61 ). Using hormone replacement, we demonstrate that E 2 is the ovarian hormone responsible for affecting satellite cells ( 60 , 61 ). Here we investigate mechanisms whereby the loss of circulating E 2 in females results in the reduced satellite cell number under normal homeostatic conditions, i.e., without any muscle injury.…”

Section: Introductionmentioning

confidence: 88%

Estradiol deficiency reduces the satellite cell pool by impairing cell cycle progression

Larson

Shams

McMillin

et al. 2022

American Journal of Physiology-Cell Physiology

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The size of the satellite cell pool is reduced in estradiol (E2)-deficient female mice and humans. Here, we use a combination of in vivo and in vitro approaches to identify mechanisms whereby E2 deficiency impairs satellite cell maintenance. By measuring satellite cell numbers in mice at several early time points post-ovariectomy (Ovx), we determine that satellite cell numbers decline by 33% between 10 and 14 days post-Ovx in tibialis anterior and gastrocnemius muscles. At 14 days post-Ovx, we demonstrate that satellite cells have a reduced propensity to transition from G0/G1 to S and G2/M phases, compared to cells from ovary-intact mice, associated with changes in two key satellite cell cycle regulators, ccna2 and p16INK4a. Further, freshly isolated satellite cells treated with E2 in vitro have 62% greater cell proliferation and require less time to complete the first division. Using clonal and differentiation assays, we measured 69% larger satellite cell colonies and enhanced satellite cell-derived myoblast differentiation with E2 treatment compared to vehicle-treated cells. Together, these results identify a novel mechanism for preservation of the satellite cell pool by E2 via promotion of satellite cell cycling.

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“…Several human studies (MacIntyre et al, 2000;Stupka et al, 2000;, but not all (Sorichter et al, 2001), report that there are sex-based differences in response to exerciseinduced muscle damage. Compared to males, females may be relatively protected against muscle damage, which may be attributed to higher concentrations of estradiol (Dieli-Conwright et al, 2009;Kitajima and Ono, 2016;Le et al, 2018;Collins et al, 2019;Larson et al, 2020). The main mechanisms believed to be responsible for estradiol's protective effects include: 1) intercalating into the cell membrane affecting fluidity/stability, 2) indirect antioxidant capacity of estradiol to reduce oxidative stress, 3) blunting of the inflammatory response, and/or 4) enhanced expansion of SC.…”

Section: Introductionmentioning

confidence: 99%

Sex-Based Differences in the Myogenic Response and Inflammatory Gene Expression Following Eccentric Contractions in Humans

et al. 2022

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After muscle injury, the interaction between muscle satellite cells (SC) and the immune response is instrumental for the repair and regeneration of skeletal muscle tissue. Studies have reported sex-based differences in the skeletal muscle inflammatory and regenerative response following injury. However, many of these studies investigated such differences by manipulating the concentration of estradiol, in rodents and humans, without directly comparing males to females. We sought to explore differences in the myogenic and inflammatory response following unaccustomed eccentric exercise in males and females. We hypothesized that females would have a blunted myogenic and inflammatory response as compared to males.Methods: 26 (13 male, 13 female) healthy young adults (22 ± 0.4 years [mean ± SEM]) performed 300 maximal eccentric contractions (180°/s) of the knee extensors. Muscle biopsies were taken before (pre) and 48 h (post) following eccentric damage. SC content and activation were determined by immunohistochemical and real time-polymerase chain reaction (rt-PCR) analysis. Inflammatory markers were analyzed using rt-PCR.Results: Following eccentric damage, males had a greater expansion of type I-associated SC (p < 0.05), and there was a trend for a greater expansion in total SC (type I + II fibers) (p = 0.06) compared to females. There was a trend for a greater increase in Pax7 and CCL2 gene expression in males compared to females (p = 0.09).Conclusion: We conclude that there are sex-based differences in the myogenic and inflammatory response, where females have a blunted SC and inflammatory response.

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Oestradiol affects skeletal muscle mass, strength and satellite cells following repeated injuries

Cited by 20 publications

References 43 publications

Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice

Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice

Estradiol deficiency reduces the satellite cell pool by impairing cell cycle progression

Sex-Based Differences in the Myogenic Response and Inflammatory Gene Expression Following Eccentric Contractions in Humans

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