Sexual dimorphism is associated with decreased  expression of processed myostatin in males

McMahon, Christopher D.; Popović, Ljiljana; Jeanplong, Ferenc; Oldham, Jenny M.; Kirk, S P; Osepchook, Claire C.; Wong, Karen; Sharma, Mridula; Kambadur, Ravi; Bass, J. J.

doi:10.1152/ajpendo.00282.2002

Cited by 57 publications

(54 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This hypothesis fits well, too, with the dearth of mitochondria, which can act as fast calcium sinks in skeletal muscle (31) as well as providing ATP for calcium uptake into the sarcoplasmic reticulum; their lack in Mstn Ϫ/Ϫ might well stimulate a compensatory formation of the sarcoplasmic reticulum. Intriguingly, small numbers of tubular aggregates are found in muscles of older male wild-type mice of the reference wild type used here and of various inbred and outbred laboratory mouse strains (32,33) but not in wild-type females, which correlates with the higher level of myostatin in wild-type female than male muscle (34).…”

Section: Discussionmentioning

confidence: 71%

Lack of myostatin results in excessive muscle growth but impaired force generation

Amthor

Macharia

Olivares-Navarrete

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

340

317

View full text Add to dashboard Cite

The lack of myostatin promotes growth of skeletal muscle, and blockade of its activity has been proposed as a treatment for various muscle-wasting disorders. Here, we have examined two independent mouse lines that harbor mutations in the myostatin gene, constitutive null ( Mstn −/− ) and compact (Berlin High Line, BEH c/c ). We report that, despite a larger muscle mass relative to age-matched wild types, there was no increase in maximum tetanic force generation, but that when expressed as a function of muscle size (specific force), muscles of myostatin-deficient mice were weaker than wild-type muscles. In addition, Mstn −/− muscle contracted and relaxed faster during a single twitch and had a marked increase in the number of type IIb fibers relative to wild-type controls. This change was also accompanied by a significant increase in type IIB fibers containing tubular aggregates. Moreover, the ratio of mitochondrial DNA to nuclear DNA and mitochondria number were decreased in myostatin-deficient muscle, suggesting a mitochondrial depletion. Overall, our results suggest that lack of myostatin compromises force production in association with loss of oxidative characteristics of skeletal muscle.

show abstract

Section: Discussionmentioning

confidence: 71%

Lack of myostatin results in excessive muscle growth but impaired force generation

Amthor

Macharia

Olivares-Navarrete

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

340

317

View full text Add to dashboard Cite

show abstract

“…The sexually dimorphic difference in GDF-11 expression coincides with the divergent growth between sexes which occurs from about six weeks of age in mice [15]. In comparison, we have shown that there are higher concentrations of mRNA and decreased mature myostatin protein in male than in female muscles and have shown that these differences are developmentally regulated by growth hormone [15,19]. The concentration of GDF-11 mRNA is higher in males than females which would seem to be inconsistent with the greater muscle mass in males than females if we assume that GDF-11 is an inhibitor of muscle development.…”

Section: Discussionmentioning

confidence: 61%

Growth and differentiation factor-11 is developmentally regulated in skeletal muscle and inhibits myoblast differentiation

Jeanplong¹,

Falconer²,

Thomas³

et al. 2012

OJMIP

Self Cite

View full text Add to dashboard Cite

Growth and differentiation factor-11 (GDF-11) is a secreted protein that is closely related to myostatin, a known inhibitor of skeletal muscle development. The role of GDF-11 in regulating skeletal muscle growth remains unclear and the pattern of expression during post-natal growth has not been reported. Therefore, we sought to determine the expression of GDF-11 during post-natal growth and its effect on myoblast proliferation and differentiation. We collected gastrocnemius muscles from male and female mice at 2, 3, 4, 6, 12, 20 and 32 weeks of age (n = 6 per sex and age). In addition, gastrocnemius muscles were collected from male wild-type and myostatin knockout mice at 4, 6, 12 and 20 weeks of age (n = 6 per age and genotype). RNA was extracted and reverse transcribed. Northern analysis identified an expected 4.4 kb mRNA transcript for GDF-11 in gastrocnemius muscles of mice. The concentration of GDF-11 mRNA, as determined by quantitative PCR, was increased in gastrocnemius muscles from 2 to 6 weeks-a period of rapid postnatal muscle growth-and remained higher in male than female mice from 4 to 20 weeks of age (P < 0.05). Interestingly, the mRNA concentration of GDF-11 and its cognate receptors (ActRIIA, ActIIB and Alk5) were increased in gastrocnemius muscles of myostatin knockout compared with wild-type mice (P < 0.05), which may suggest a compensatory mechanism for the lack of myostatin. In support, recombinant GDF-11 inhibited differentiation of C 2 C 12 murine myoblasts and those isolated from myostatin knockout and wild-type mice (P < 0.05). Inhibited differentiation of C 2 C 12 myoblasts was associated with decreased mRNA expression of early and late molecular markers of differentiation (MyoD, myogenin, IGF-II, desmin and MyHC, P < 0.05). Our results suggest that GDF-11 regulates growth of skeletal muscles by inhibiting myoblast differentiation in an autocrine/paracrine manner and, perhaps, also plays a role in regulating sexually dimorphic growth.

show abstract

“…Although the precise mechanisms that account for these gender differences in myostatin effects are unknown, these data suggest that there may be gender-specific mechanisms that can override the effects of myostatin on muscle mass in female transgenic mice. This interpretation is supported by the recent demonstration that decreased abundance of processed myostatin in young wild-type mice is associated with increased body mass and skeletal muscle mass in male compared with female animals (22). It is possible that association with other proteins, more abundant in females than in males, may partially inactivate myostatin in females despite the higher levels seen in this sex, as has been shown to occur in transgenic mice overexpressing follistatin (17).…”

Section: Discussionmentioning

confidence: 72%

Lower skeletal muscle mass in male transgenic mice with muscle-specific overexpression of myostatin

Reisz‐Porszasz¹,

Bhasin²,

Artaza³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

285

213

View full text Add to dashboard Cite

Cadavid. Lower skeletal muscle mass in male transgenic mice with muscle-specific overexpression of myostatin. Am J Physiol Endocrinol Metab 285: E876-E888, 2003. First published June 24, 2003 10.1152 10. /ajpendo.00107.2003 in the myostatin gene are associated with hypermuscularity, suggesting that myostatin inhibits skeletal muscle growth. We postulated that increased tissue-specific expression of myostatin protein in skeletal muscle would induce muscle loss. To investigate this hypothesis, we generated transgenic mice that overexpress myostatin protein selectively in the skeletal muscle, with or without ancillary expression in the heart, utilizing cDNA constructs in which a wild-type (MCK/Mst) or mutated muscle creatine kinase (MCK-3E/Mst) promoter was placed upstream of mouse myostatin cDNA. Transgenic mice harboring these MCK promoters linked to enhanced green fluorescent protein (EGFP) expressed the reporter protein only in skeletal and cardiac muscles (MCK) or in skeletal muscle alone (MCK-3E). Seven-week-old animals were genotyped by PCR of tail DNA or by Southern blot analysis of liver DNA. Myostatin mRNA and protein, measured by RT-PCR and Western blot, respectively, were significantly higher in gastrocnemius, quadriceps, and tibialis anterior of MCK/Mst-transgenic mice compared with wild-type mice. Male MCK/Mst-transgenic mice had 18-24% lower hind-and forelimb muscle weight and 18% reduction in quadriceps and gastrocnemius fiber cross-sectional area and myonuclear number (immunohistochemistry) than wild-type male mice. Male transgenic mice with mutated MCK-3E promoter showed similar effects on muscle mass. However, female transgenic mice with either type of MCK promoter did not differ from wild-type controls in either body weight or skeletal muscle mass. In conclusion, increased expression of myostatin in skeletal muscle is associated with lower muscle mass and decreased fiber size and myonuclear number, decreased cardiac muscle mass, and increased fat mass in male mice, consistent with its role as an inhibitor of skeletal muscle mass. The mechanism of gender specificity remains to be clarified. sarcopenia; wasting; skeletal muscle growth A NUMBER OF GENETIC FACTORS, growth factors, hormones, and nutritional factors are important in the regulation of skeletal muscle mass; however, their precise role in the integrated, in vivo regulation of skeletal muscle homeostasis and muscle wasting associated with chronic illness and aging remains poorly understood. Considerable interest has focused recently on the role of myostatin, or growth differentiation factor (GDF) 8 (16, 35), a novel regulator of muscle mass that is produced predominantly in the skeletal muscle. A targeted deletion of the entire COOH terminus of myostatin (23) or a selected natural mutation leading to a truncated and inactive myostatin protein (38) causes a considerable increase in muscle mass in mice. Naturally occurring mutations in certain breeds of cattle that elicit an out-of-frame truncated protein or an inactive full-length protein ...

show abstract

Sexual dimorphism is associated with decreased expression of processed myostatin in males

Cited by 57 publications

References 26 publications

Lack of myostatin results in excessive muscle growth but impaired force generation

Lack of myostatin results in excessive muscle growth but impaired force generation

Growth and differentiation factor-11 is developmentally regulated in skeletal muscle and inhibits myoblast differentiation

Lower skeletal muscle mass in male transgenic mice with muscle-specific overexpression of myostatin

Contact Info

Product

Resources

About