Roles of Estrogen, Estrogen Receptors, and Estrogen-Related Receptors in Skeletal Muscle: Regulation of Mitochondrial Function

Yoh, Kenta; Ikeda, Kazuhiro; Horie, Kuniko; Inoue, Satoshi

doi:10.3390/ijms24031853

Cited by 33 publications

(25 citation statements)

References 102 publications

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“…This variation in response might stem from the effects of sex hormones such as estrogen on skeletal muscle. Given the presence of estrogen receptors within skeletal muscle and the effects of estrogen on skeletal muscle strength (Collins et al ., 2019), mitochondrial function (Pellegrino et al ., 2022; Yoh et al ., 2023), and regenerative capacity (Kitajima & Ono, 2016; Pellegrino et al ., 2022), estrogen has a clear effect on skeletal muscle cellular function through modification of intracellular proteins. In fact, estradiol has been shown to directly affect regulatory light chain function in skeletal muscle (Lai et al ., 2016), prompting the possibility that estrogen might also affect the function of other intracellular proteins, such as titin.…”

Section: Discussionmentioning

confidence: 99%

Fatiguing Exercise Reduces Cellular Passive Young’s Modulus in Human Vastus Lateralis Muscle

Privett,

Ricci,

David

et al. 2024

Preprint

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Previous studies demonstrated that acute, exercise-induced fatigue transiently reduces whole-muscle stiffness. Because reduced muscle stiffness at fatigue may contribute to increased injury risk and impaired contractile performance, the present study seeks to elucidate potential intracellular mechanisms underlying these reductions. To that end, cellular passive Young's Modulus was measured in single, permeabilized muscle fibers from healthy, recreationally-active males and females. Eight volunteers (4 male, 4 female) completed unilateral, repeated maximal voluntary knee extensions until fatigue, after which percutaneous needle biopsies were performed on the fatigued (F) and non-fatigued (NF) Vastus Lateralis muscles. Muscle samples were processed for mechanical assessment and separately for imaging and phosphoproteomics. Single fibers were passively (pCa 8.0), incrementally stretched to 156% of the initial sarcomere length to assess Young's Modulus, calculated as the slope of the resulting stress-strain curve at short (strain = 1.00-1.24 %Lo) and long (strain = 1.32-1.56 %Lo) fiber lengths. Titin phosphorylation was assessed by liquid chromatography followed by high-resolution mass spectrometry (LC-MS). Passive modulus was significantly reduced by fatigue at short and long lengths in male, but not female, participants. Fatigue increased phosphorylation of four serine residues located within the elastic region of titin and reduced phosphorylation at one serine residue but did not impact active tension nor sarcomere ultrastructure. Collectively, these results suggest muscle fatigue reduces cellular passive modulus in young males, but not females, concurrent with altered titin phosphorylation. These results provide mechanistic insight contributing to the understanding of sex-based differences in soft tissue injury and falls risk.

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Section: Discussionmentioning

confidence: 99%

Fatiguing Exercise Reduces Cellular Passive Young’s Modulus in Human Vastus Lateralis Muscle

Privett,

Ricci,

David

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…It is well established that F animals have a greater exercise capacity than M, and this enhanced endurance performance in F is regulated, in part, by estrogen (37). This hormone induces target gene expression by binding to estrogen receptor α and estrogen-related receptor α, both playing crucial roles in the plasticity of skeletal muscle mass, function, as well as repair and regeneration (38). Estrogen exerts its effects on transcription via the CARM1-mediated arginine methylation of histone and nonhistone proteins (39).…”

Section: Discussionmentioning

confidence: 99%

Sex-Specific Effect of CARM1 in Skeletal Muscle Adaptations to Exercise

VANLIESHOUT,

STOUTH,

RAZIEE

et al. 2023

Medicine &Amp; Science in Sports &Amp; Exercise

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Purpose The purpose of this study was to determine how the intersection of coactivator-associated arginine methyltransferase 1 (CARM1) and biological sex impacts skeletal muscle adaptations to chronic physical activity. Methods 12-week-old female (F) and male (M) wild-type (WT) and CARM1 skeletal muscle-specific knockout mice (mKO) were randomly assigned to sedentary (SED) or voluntary wheel running (VWR) experimental groups. For 8 weeks, the animals in the VWR cohort had volitional access to running wheels. Subsequently, we performed whole-body functional tests, and 48 hours later muscles were harvested for molecular analysis. Western blotting, enzyme activity assays, as well as confocal and transmission electron microscopy (TEM) were used to examine skeletal muscle biology. Results Our data reveal a sex-dependent reduction in VWR volume caused by muscle-specific ablation of CARM1, as F CARM1 mKO mice performed less chronic, volitional exercise than their WT counterparts. Regardless of VWR output, exercise-induced adaptations in physiological function were similar between experimental groups. A broad panel of protein arginine methyltransferase (PRMT) biology measurements, including markers of arginine methyltransferase expression and activity, were unaffected by VWR, except for CARM1 and PRMT7 protein levels, which decreased and increased with VWR, respectively. Changes in myofiber morphology and mitochondrial protein content showed similar trends among animals. However, a closer examination of TEM images revealed contrasting responses to VWR in CARM1 mKO mice compared to WT littermates, particularly in mitochondrial size and fractional area. Conclusions The present findings demonstrate that CARM1 mKO reduces daily running volume in F mice, as well as exercise-evoked skeletal muscle mitochondrial plasticity, which indicates that this enzyme plays an essential role in sex-dependent differences in exercise performance and mitochondrial health.

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“…17,20,35 Mechanistically, this is explained in mice by findings showing that estradiol reduces mitochondrial membrane viscosity and thereby improves the complexes' mobility and activity, thus increasing the rate of electron transfer. 17 However, most previous studies, 18,[36][37][38] but not all, 17,20 suggest that estradiol enhances MRC by increasing mitochondrial biogenesis via activation of the estrogen-receptor-α (ERα) pathway. In line with these studies, the HT group in the present study showed a significantly higher CS activity in skeletal muscle tissue.…”

Section: Mitochondrial Functionmentioning

confidence: 99%

Metabolic flexibility in postmenopausal women: Hormone replacement therapy is associated with higher mitochondrial content, respiratory capacity, and lower total fat mass

Kleis‐Olsen,

Farlov,

Petersen

et al. 2024

Acta Physiologica

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AimTo investigate effects of hormone replacement therapy in postmenopausal women on factors associated with metabolic flexibility related to whole‐body parameters including fat oxidation, resting energy expenditure, body composition and plasma concentrations of fatty acids, glucose, insulin, cortisol, and lipids, and for the mitochondrial level, including mitochondrial content, respiratory capacity, efficiency, and hydrogen peroxide emission.Methods22 postmenopausal women were included. 11 were undergoing estradiol and progestin treatment (HT), and 11 were matched non‐treated controls (CONT). Peak oxygen consumption, maximal fat oxidation, glycated hemoglobin, body composition, and resting energy expenditure were measured. Blood samples were collected at rest and during 45 min of ergometer exercise (65% VO2peak). Muscle biopsies were obtained at rest and immediately post‐exercise. Mitochondrial respiratory capacity, efficiency, and hydrogen peroxide emission in permeabilized fibers and isolated mitochondria were measured, and citrate synthase (CS) and 3‐hydroxyacyl‐CoA dehydrogenase (HAD) activity were assessed.ResultsHT showed higher absolute mitochondrial respiratory capacity and post‐exercise hydrogen peroxide emission in permeabilized fibers and higher CS and HAD activities. All respiration normalized to CS activity showed no significant group differences in permeabilized fibers or isolated mitochondria. There were no differences in resting energy expenditure, maximal, and resting fat oxidation or plasma markers. HT had significantly lower visceral and total fat mass compared to CONT.ConclusionUse of hormone therapy is associated with higher mitochondrial content and respiratory capacity and a lower visceral and total fat mass. Resting energy expenditure and fat oxidation did not differ between HT and CONT.

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Roles of Estrogen, Estrogen Receptors, and Estrogen-Related Receptors in Skeletal Muscle: Regulation of Mitochondrial Function

Cited by 33 publications

References 102 publications

Fatiguing Exercise Reduces Cellular Passive Young’s Modulus in Human Vastus Lateralis Muscle

Fatiguing Exercise Reduces Cellular Passive Young’s Modulus in Human Vastus Lateralis Muscle

Sex-Specific Effect of CARM1 in Skeletal Muscle Adaptations to Exercise

Metabolic flexibility in postmenopausal women: Hormone replacement therapy is associated with higher mitochondrial content, respiratory capacity, and lower total fat mass

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