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

Brown, Marybeth; Ning, Jie; Ferreira, J. Andries; Bogener, Jennifer L.; Lubahn, Dennis B.

doi:10.1152/ajpendo.90696.2008

Cited by 55 publications

(54 citation statements)

References 53 publications

(43 reference statements)

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“…In addition, this positive relationship was unrelated to the testosterone level as the association persisted after its adjustment ( Table 2). The role of estrogen receptor activation in the modulation of muscle mass remains unclear although some animal studies have revealed that estrogen receptor activation was involved in this process (32)(33)(34). Our results also revealed that total E 2 level, though positively related to muscle mass, was negatively related to muscle strength (Tables 2 and 4), in contrary to testosterone that was associated favorably with both muscle quantity and quality.…”

Section: Discussionsupporting

confidence: 45%

Testosterone but not estradiol level is positively related to muscle strength and physical performance independent of muscle mass: a cross-sectional study in 1489 older men

Auyeung¹,

Lee²,

Kwok³

et al. 2011

European Journal of Endocrinology

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Objective: To examine the relationship between different measures of testosterone and estradiol (E 2 ), muscle mass, muscle strength, and physical performance; and to test whether the association of sex hormone level with muscle strength and physical performance was independent of muscle mass. Design and methods: A cross-sectional survey on 1489 community-dwelling men older than 64 years of age. Serum levels of testosterone and E 2 were measured by mass spectrometry, and sex hormonebinding globulin (SHBG) levels were measured by immunoradioassay. Muscle mass was examined by dual-energy X-ray absorptiometry and physical performance was assessed by hand-grip strength, gait speed, step length and chair-stand test. Results: Appendicular skeletal mass (ASM) was positively associated with total testosterone (TT; P!0.001), free testosterone (FT; P!0.001), and total E 2 (P!0.001) but not with free E 2 (PZ0.102). After adjustment for age, serum SHBG and relative ASM, both TT and FT were significantly associated with grip strength, narrow-walk speed and the composite neuromuscular score. Higher total E 2 , but not free E 2 was associated with lower grip strength (P!0.05) after adjustment for age, FT, SHBG and relative ASM. Conclusions: Testosterone level was related to both muscle mass, strength and physical performance. Total E 2 level, though related to muscle mass positively, affected muscle strength adversely in older men. European Journal of Endocrinology 164 811-817 IntroductionSeveral studies have examined the inter-relationship between various measures of testosterone level, muscle mass and muscle strength (1-6). In men aged 65 or older, Baumgartner et al.(1) reported that free testosterone index, but not total testosterone (TT) level, was modestly associated with muscle mass, whereas Iannuzzi-Sucich et al. (2) demonstrated that muscle mass was correlated to bioavailable testosterone (BioT), leg strength and physical performance. However, in another cohort of healthy older men, Van den Beld et al. (3) reported that testosterone level, as represented by TT and BioT, was related to muscle strength but not to muscle mass. On the other hand, Roy et al. (5) observed that TT and BioT were positively correlated with both the muscle mass and strength, yet after adjustment for muscle mass, they were no longer independently associated with muscle strength. Szulc et al. (4) had compared the muscle mass and physical performance of hypogonadal and eugonadal men and found that hypogonadal men exhibited impaired static and dynamic balance despite relatively preserved muscle mass. Similarly, Orwoll et al. (6) have observed that testosterone level was related to physical performance and fall risk but not to muscle mass. Although the effect of testosterone supplementation on muscle mass and strength was less controversial in interventional studies (7-14), whether endogenous testosterone was related to muscle mass alone, muscle strength alone, or both; and which measures of endogenous testosterone best related to muscle ...

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Section: Discussionsupporting

confidence: 45%

Testosterone but not estradiol level is positively related to muscle strength and physical performance independent of muscle mass: a cross-sectional study in 1489 older men

Auyeung¹,

Lee²,

Kwok³

et al. 2011

European Journal of Endocrinology

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“…It was recently demonstrated that ERa activation is required for normal muscle mass in male mice (31). In addition, there are indications that both ERa and ERb activation modulate muscle mass and/or function in mice (32,33). We also previously showed that E 2 , but not dihydrotestosterone, increased lean mass in orchidectomized, aged male rats (34).…”

Section: Discussionmentioning

confidence: 85%

“…Clinical trials investigating the effects of aromatase inhibition in older men showed no effect of the intervention on body composition or muscle strength (29,30) and, thus, did not support an important role of serum E 2 levels for lean mass in men. Nevertheless, animal studies have indicated that not only AR activation but also ER activation modulates lean mass (31)(32)(33)(34). It was recently demonstrated that ERa activation is required for normal muscle mass in male mice (31).…”

Section: Discussionmentioning

confidence: 99%

Serum estradiol is associated with lean mass in elderly Swedish men

Vandenput

Mellström

Karlsson

et al. 2010

European Journal of Endocrinology

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Objective: Association studies in men have shown that androgens are inversely related to fat measures, while the relation between sex steroids and lean mass remains unclear. We, therefore, investigated the associations between serum sex steroid levels and body composition in elderly men with a main focus on lean mass measures. Design and methods: A cross-sectional survey of a population-based cohort of 3014 elderly men, aged 69-80 years (Osteoporotic Fractures in Men study, Sweden). Serum levels of testosterone and estradiol (E 2 ) were measured by mass spectrometry, sex hormone-binding globulin (SHBG) levels were measured by IRMA, and measures of body composition were obtained by dual-energy X-ray absorptiometry. Results: Total as well as free serum testosterone associated independently inversely (P!0.001), while total as well as free serum E 2 associated independently directly (P!0.001) with total body fat mass and trunk fat mass. Serum SHBG associated independently inversely with central fat distribution. Serum E 2 and free E 2 but not serum testosterone or free testosterone levels associated positively with lean mass (P!0.01). Elderly men within the lowest quartile of free E 2 had 0.5 kg less lean mass in the legs than subjects within the highest quartile, while the subjects in the different quartiles of free testosterone did not differ in lean mass. Conclusions: Serum E 2 , but not serum testosterone, is directly associated with lean mass in this large study of elderly Swedish men. In addition, serum SHBG is associated with central fat distribution and we confirmed that serum testosterone is inversely associated with fat mass.

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“…OVX rats fail to efficiently recover muscle mass after unloading followed by reloading compared with OVX rats treated with estrogens (McClung et al 2006, Sitnick et al 2006, suggesting that estrogens are important for muscle regrowth. By contrast, estrogen receptor alpha (Erα (Esr1))-, but not Erβ (Esr2)-knockout female mice display a significant increase in absolute muscle weight (Brown et al 2009). However, such ERα inactivation results in a decrease in the muscle peak tetanic tension per CSA (Brown et al 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Because accumulating evidence suggests that estrogens favor muscle regeneration after injury (Brown et al 2009, Velders et al 2012, we next determined the effects of prolonged estrogen insufficiency on satellite cell numbers and functions at 24 weeks after ovariectomy.…”

Section: Muscle Stem Cell Functions Are Impaired In An Estrogen-deficmentioning

confidence: 99%

Estrogens maintain skeletal muscle and satellite cell functions

Kitajima

Ono

2016

Journal of Endocrinology

124

115

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Estrogens have crucial roles in an extensive range of physiological functions regulating cellular proliferation and differentiation, development, homeostasis, and metabolism. Therefore, prolonged estrogen insufficiency influences various types of tissues expressing estrogen receptors (ERs). Although ERs are expressed in skeletal muscle and its stem cells, called satellite cells, how prolonged estrogen insufficiency affects their function remains unclear. In this study, we investigated the effect of estrogen reduction on muscle in young ovariectomized (OVX) female mice. We found that reduced estrogens resulted in muscle atrophy in a time-dependent manner. Muscle force generation was reduced in OVX mice. Interestingly, prolonged estrogen insufficiency shifted fiber types toward faster myosin heavy chain isoforms. The number of satellite cells per isolated myofiber was unchanged, while satellite cell expansion, differentiation, and self-renewal were all markedly impaired in OVX mice. Indeed, muscle regeneration was significantly compromised in OVX mice. Taken together, our results demonstrate that estrogens are essential for comprehensively maintaining muscle function with its insufficiency affecting muscle strength and regeneration in young female mice.

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

Cited by 55 publications

References 53 publications

Testosterone but not estradiol level is positively related to muscle strength and physical performance independent of muscle mass: a cross-sectional study in 1489 older men

Testosterone but not estradiol level is positively related to muscle strength and physical performance independent of muscle mass: a cross-sectional study in 1489 older men

Serum estradiol is associated with lean mass in elderly Swedish men

Estrogens maintain skeletal muscle and satellite cell functions

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