Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition

In the paper

“For example, MyHC-IIa expression is higher in males vs. females in the soleus (58% in males vs. 36% in females) and tibialis anterior (TA) (39% in males vs. 25% in females), whereas in the plantaris, IIa expression is higher in females (37%) than in males (16%).”

In the paper

“The mouse masseter is composed of high numbers of IIX fibers in both sexes; however, there are threefold fewer IIB fibers and more IIA fibers in females compared with males (27).”

What the sources say

• Not checked yetcites [27] source

In the paper

“Analysis of mRNA from both male and female vastus lateralis biopsies by microarray shows (when normalized to α-actinin) that the female muscle has 35% more MyHC-I/β, 30% less MyHC-IIa, and 15% less MyHC-IIx mRNA than the corresponding male muscle (96).”

What the sources say

• Not checked yetcites [96] source

In the paper

“There are 11 myosin heavy chain (MyHC) genes that encode different myosin isoforms in mammals (77).”

What the sources say

• Not checked yetcites [77] source

In the paper

“Type-I fibers account for 36% of the total biopsy area in men and 44% in women, whereas type-IIA fibers account for 41% in men and only 34% in women (89).”

What the sources say

• Not checked yetcites [89] source

In the paper

“Functionally, MyHC isoform expression directly affects muscle fiber-type contractile velocity via myosin ATPase activity (74), with relative velocities of I < IIA < IIX < IIB (73, 74).”

What the sources say

• Not checked yetcites [74] source
• Not checked yetcites [73] Reiser PJ, 1985, J Biol Chem source

In the paper

“In contrast, human skeletal muscle does not express MyHC-IIb protein, a phenomenon that appears to be, at least in part, due to a reduction in the activity of the human MyHC-IIb promoter region (37).”

What the sources say

• Not checked yetcites [37] source

In the paper

“Overall, in this analysis, the average MyHC isoform percentages in the male vastus lateralis are IIx (20%), IIa (46%), and I (34%), whereas the females samples are IIx (23%), IIa (36%), and I (41%) (89).”

What the sources say

• Not checked yetcites [89] source

In the paper

“Overall, evidence to date suggests that skeletal muscle fiber-type composition is dependent on species, anatomical location/function, and sex.”

In the paper

“Male rabbit masseter is comprised of nearly 80% type-IIA fibers, whereas the female masseter contains only ∼50% (28).”

What the sources say

• Not checked yetcites [28] source

In the paper

“Treatment of euthyroid animals with T3 induces hyperthyroidism, producing a reversible slow-to-fast MyHC isoform transition from I → IIa → IIx → IIb (for review, see Ref. 78).”

What the sources say

• Not checked yetcites [78] source

In the paper

“These studies suggest a potential role for T3 in skeletal muscle contractility and in sex-based differences that may exist in the response to changing T3 levels but point to the need for further investigations.”

In the paper

“In fact, hormonal regulation of skeletal muscle development and contractility are well documented (29, 70).”

What the sources say

• Not checked yetcites [29] source
• Not checked yetcites [70] source

In the paper

“Endurance is longer in women (15 min) compared with men (8 min), and after reaching exhaustion, recovery occurs faster in women than in men (31).”

What the sources say

• Not checked yetcites [31] source

In the paper

“T3 treatment in euthyroid animals leads to a conversion from IIA to IIB fibers in the EDL of young and old female rats vs. no transition in males (52).”

What the sources say

• Not checked yetcites [52] source

In the paper

“Thyroid hormone (T3) can regulate MyHC gene expression (42).”

What the sources say

• Not checked yetcites [42] source

In the paper

“These studies suggest that force generation and relaxation are faster during fatigue in men compared with women, whereas endurance is higher and recovery is quicker in women than in men.”

In the paper

“During menopause, the decline in estrogen levels is paralleled with a slight increase in injury risk and a decline in lean body mass (9).”

What the sources say

• Not checked yetcites [9] source

In the paper

“Specifically, after treatment with T3, male rat soleus muscle expresses 73% type-I/IIA and 26% type-I/IIAX of the total fibers, whereas females express 37% type-I, 49% type-I/IIA, and only 6% type-I/IIAX fibers (101).”

What the sources say

• Not checked yetcites [101] source

In the paper

“Hypothyroid females appear to have a higher proportion of type-II fibers compared with hypothyroid males; however, type-II fiber atrophy occurs in hypothyroid female patients but not in males (63).”

What the sources say

• Not checked yetcites [63] source

In the paper

“Four weeks of T3 treatment induces an increase in type-IIA fibers and a downregulation of type-I fibers in male and female rat soleus muscle (57, 101).”

What the sources say

• Not checked yetcites [57] source
• Not checked yetcites [101] source

In the paper

“Overall, the increase in IIX content from the type-I/IIAX fibers is greater in young T3-treated males (21%) than females (10%), and the upregulation of IIA is greater in young females (43%) than in young males (27%) (101).”

What the sources say

• Not checked yetcites [101] source

In the paper

“After intermittent bouts of isometric contraction (5 s on and 5 s off) in the adductor pollicis muscle, women fatigue more slowly and to a smaller degree than men (31).”

What the sources say

• Not checked yetcites [31] source

In the paper

“In another study of euthyroid animals, treatment with T3 induces expression of IIX in the soleus of aged male rats (4–15%), whereas there is no detectable IIX in females at any age (52).”

What the sources say

• Not checked yetcites [52] source

In the paper

“These studies highlight the differences in fiber-type conversion as it relates to sex and pinpoints the differences in IIx expression in males and females.”

In the paper

“Animal models of low estrogen levels, which occur after ovariectomy (OVX), reveal an increase in overall body mass and in the mass of individual muscles (68).”

What the sources say

• Not checked yetcites [68] source

In the paper

“Although forces exerted by both young men and women are not significantly different, endurance is lower for men than for women (11 vs. 18 min) (39).”

What the sources say

• Not checked yetcites [39] source

In the paper

“OVX leads to an increase in overall body weight and muscle weight (68), and a 70% increase in ERα mRNA with no change in ERβ mRNA (7).”

What the sources say

• Not checked yetcites [68] source
• Not checked yetcites [7] source

In the paper

“Estrogen has been shown to influence fiber size, overall muscle weight, muscle regeneration, and contractility, and to induce minimal changes in fiber-type distribution.”

In the paper

“Overall, ERβ deletion increases the contractile time and decreases the speed of contractile kinetics in both males and females.”

In the paper

“This decline in regenerative capacity is thought to be directly related to findings that estrogen is associated with maintenance of muscle strength in pre- and postmenopausal women (69) and suggests a role for ERs in skeletal muscle maintenance (64, 84, 85, 88).”

What the sources say

• Not checked yetcites [69] source
• Not checked yetcites [64] source
• Not checked yetcites [84] source

In the paper

“The fraction of strong binding myosin in OVX muscle is 0.263 or ∼15% lower than baseline (67, 68). Following estrogen treatment, the fraction of strongly bound myosin increases to 0.311, which is indistinguishable from sham levels (0.300) (67).”

What the sources say

• Not checked yetcites [67] source
• Not checked yetcites [68] source

In the paper

“Relaxation time during a basic contraction in the soleus is significantly shorter in wild-type males (104 ms) than in females (158 ms) and in null males (104 ms) compared with null females (191 ms).”

What the sources say

• Not checked yetcites [33] source

In the paper

“Because of the OVX-induced decrease in tetanic force, which requires rapid replenishment and utilization of calcium stores, and the increase in fiber diameter, which could compensate for a decline in calcium sensitivity, calcium handling and sensitivity may be playing a role in the regulation of contractile differences in samples with and without estrogen.”

In the paper

“Ronkainen et al. (76) found that HRT is associated with better mobility, greater muscle power, and favorable body and muscle composition in women ages 54–62 (76).”

What the sources say

• Not checked yetcites [76] source

In the paper

“Analysis of contractile function in OVX mice reveals a significant decrease in maximal isometric tetanic force from sham levels (180 mN) to 168 mN (67, 68). This decline is attenuated to 187 mN with estrogen supplementation (67).”

What the sources say

• Not checked yetcites [67] source
• Not checked yetcites [68] source

In the paper

“In the studies referenced in the previous sections, there is no change in MyHC isoform expression or overall muscle fiber-type composition, but there are estrogen-related changes in fiber-type diameter, muscle size, contractility, and the actin-myosin interaction.”

In the paper

“In rat soleus and EDL muscles, OVX leads to a slight increase in the mean fiber diameter of type-I, -IIA, and -IIB fibers. Estrogen supplementation decreases fiber diameter in all fiber types in both the soleus and EDL significantly from OVX levels to below baseline levels (90).”

What the sources say

• Not checked yetcites [90] source

In the paper

“In male and female vastus lateralis muscle, expression of ERα mRNA is 180-fold higher than ERβ, with no significant difference in expression levels between males and females (98).”

What the sources say

• Not checked yetcites [98] source

In the paper

“OVX induces a reduction in time to peak tension and increases time to 50% relaxation in rats, whereas estrogen replacement reverses the OVX-induced reduction in peak tension (62).”

What the sources say

• Not checked yetcites [62] source

In the paper

“Skeletal muscle expresses two forms of ERs (α and β), and the effects of estrogen are mediated, in part, through these receptors (14, 21, 56, 98).”

What the sources say

• Not checked yetcites [14] source
• Not checked yetcites [21] source
• Not checked yetcites [56] source

In the paper

“Studies on muscle repair following exercise-induced injury highlight a sex-based difference in which higher levels of muscle creatine kinase (indicative of injury) are observed in male than in female rats following injury. Following OVX, levels of muscle creatine kinase in females are similar to levels in injured males (3, 4, 8).”

What the sources say

• Not checked yetcites [3] source
• Not checked yetcites [4] source
• Not checked yetcites [8] source

In the paper

“As stated previously, there is no sexually dimorphic expression in either ERα or ERβ in skeletal muscle (98).”

What the sources say

• Not checked yetcites [98] source

In the paper

“Following a fatiguing protocol on soleus and EDL muscle, force decreases less in ERβ−/− males than in wild-type males, whereas the reverse is true for females, suggesting a role for ERβ knockout in enhancing endurance in males and reducing endurance in females (33).”

What the sources say

• Not checked yetcites [33] source

In the paper

“Recent studies suggest a beneficial role for hormone replacement therapy (HRT), supplementation with estrogen and progesterone, and the induction of pathways by which estrogen can aide in skeletal muscle maintenance and repair (71).”

What the sources say

• Not checked yetcites [71] source

In the paper

“ERα-null mice have a decreased muscle regenerative capacity following injury, as evidenced by small myofibers and centrally located nuclei (50).”

What the sources say

• Not checked yetcites [50] source

In the paper

“Taken together, these findings on estrogen and the ER-mediated regulation of the contractile response and fiber-type distribution suggest a role for estrogen and its receptors in contractile maintenance and function, with a differential effect of estrogen in males vs. females.”

In the paper

“In mice, castration produces a decrease in body weight, which is attenuated with testosterone supplementation, and although overall muscle weight increases, the fiber CSA of the soleus and TA do not significantly change (6).”

What the sources say

• Not checked yetcites [6] source

In the paper

“With advancing age, testosterone levels drop, and testosterone deficiency is associated with early death, primarily from cardiovascular disease, a decrease in muscle mass and/or strength, and sexual dysfunction (46).”

What the sources say

• Not checked yetcites [46] source

In the paper

“ARs are widely expressed in myoblasts, myofibers, and motoneurons in both males and females (17, 100), and testosterone injected into the masseter of female guinea pigs leads to an increase in fiber size (35).”

What the sources say

• Not checked yetcites [17] source
• Not checked yetcites [100] source
• Not checked yetcites [35] Gutmann E, 1970, Histochemistry source

In the paper

“Testosterone is a highly studied androgen that is associated with an increase in muscle mass (66, 83).”

What the sources say

• Not checked yetcites [66] source
• Not checked yetcites [83] source

In the paper

“Testosterone has been shown to induce its effects through binding to intracellular androgen receptors (ARs) (34), which then regulate gene transcription (18, 81).”

What the sources say

• Not checked yetcites [34] source
• Not checked yetcites [18] source
• Not checked yetcites [81] Simental JA, 1991, J Biol Chem source

In the paper

“Analysis of fiber-type distribution in hypogonadal males vs. females reveals no significant changes in type-I, -IIA, -IIX, or -IIB fibers in gastrocnemius muscle or in type-I or -IIA fibers in the soleus (79).”

What the sources say

• Not checked yetcites [79] source

In the paper

“Additionally, in AR-null males, force production decreases in fast-twitch fibers, whereas fatigue resistance increases in slow-twitch fibers to levels similar to wild-type females (59).”

What the sources say

• Not checked yetcites [59] source

In the paper

“In mice, castration produces a decrease in body weight, which is attenuated with testosterone supplementation, and although overall muscle weight increases, the fiber CSA of the soleus and TA do not significantly change (6).”

What the sources say

• Not checked yetcites [6] source

In the paper

“Additionally fiber-type distribution of the gastrocnemius is relatively unchanged from wild-type mice, with I < IIX < IIA < IIB being the relative contribution of each fiber-type in males and females (79).”

What the sources say

• Not checked yetcites [79] source

In the paper

“As mentioned earlier, studies of vastus lateralis biopsies show fiber-type CSA to be larger in men than in women. Specifically, type-I fibers are 19% larger, type-IIA fibers are 59% larger, and type-IIX fibers are 66% larger in men than in women (normalized to total biopsy section analyzed) (89).”

What the sources say

• Not checked yetcites [89] source

In the paper

“These anabolic effects of testosterone are well characterized and provide the catalysts for further investigation of the response of muscle fiber-type composition to testosterone deficiency and supplementation in males and females.”

In the paper

“During fatigue, where females typically have greater endurance, ERβ elimination decreases the endurance in the female and enhances endurance in the male.”

In the paper

“Testosterone supplementation leads to an increase in muscle mass and a decrease in fat content in hypogonadal men (13).”

What the sources say

• Not checked yetcites [13] Brodsky IG, 1996, J Clin Endocrinol Metab

In the paper

“GRB10 knockout in male and female mice produces an increase in muscle weight and a decrease in body fat percentage and thus enhances muscularity (86).”

What the sources say

• Not checked yetcites [86] source

In the paper

“Testosterone deficiency leads to a decline in body mass, a decrease in fast-twitch fiber diameter, a conversion to slow-twitch fibers, and enhanced fatigue resistance in males but not females.”

In the paper

“In this study, the authors focus on two particular genes that are upregulated in women compared with men and that are known to code for proteins that are in signaling pathways of growth factors known to regulate muscle mass: growth factor receptor-bound protein 10 (GRB10) and activin receptor type-2A (ACVR2A).”

What the sources say

• Not checked yetcites [96] source

In the paper

“Although thyroid hormone induces a conversion from slow to fast fibers and increases contractile velocity, sex-specific hormones estrogen and testosterone are implicated in skeletal muscle growth, fiber size, and minimally in contractile function.”

In the paper

“Sex-based differences in skeletal muscle fiber-type composition and function are apparent in numerous species and are present in specific anatomical locations.”

In the paper

“There is a prevalence of slower type-I and -IIA fibers in females compared with males that parallels the lower contractile velocity in females compared with males.”

In the paper

“Because aromatase converts testosterone to estrogen (60), testosterone can induce its effects via either ERs or ARs, thus this contractile effect is thought to be mediated by the activation of ERs.”