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Updated: Sep 3, 2025
Skeletal Muscle Gender Dimorphism from Proteomics
Published on: December 14, 2011
Sexual Dimorphism in Transcriptional and Functional Glucocorticoid Effects on Mouse Skeletal Muscle
Sheng Li1,2, Milena Schönke1,2, Jacobus C Buurstede1,2
1Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, Netherlands.
Abstract:
Muscle atrophy is common in patients with increased glucocorticoid exposure. Glucocorticoid effects are often sex-specific, and while different glucocorticoid responses between male and female subjects are reported, it is unclear why this is. In this study, we evaluated the effects of corticosterone and synthetic glucocorticoid treatment on muscle atrophy in male and female mice. We found that corticosterone treatment reduced grip strength in female mice only, whereas muscle mass was reduced in both sexes. Skeletal muscle transcriptional responses to corticosterone treatment were more pronounced and widespread in male mice. Synthetic glucocorticoid treatment reduced grip strength in both sexes, while female mice were more sensitive to muscle atrophy than male mice. To evaluate the role of androgens, chemically-castrated male mice were treated with synthetic glucocorticoids. We observed additively reduced muscle mass, but did not observe any interaction effects. Although sex differences in glucocorticoid responses in skeletal muscle are partly influenced by androgen signaling, further studies are warranted to fully delineate the underlying mechanisms.
Insights
Glucocorticoids cause muscle atrophy differently in male and female mice, with sex hormones playing a partial role in these varied responses.
Area of Science:
- Endocrinology
- Muscle Physiology
- Molecular Biology
Background:
- Increased glucocorticoid exposure is a common cause of muscle atrophy.
- Glucocorticoid effects on muscle can be sex-specific, but the underlying mechanisms remain unclear.
Purpose of the Study:
- To investigate sex-specific effects of glucocorticoids on muscle atrophy in mice.
- To explore the role of androgens in mediating glucocorticoid-induced muscle atrophy.
Main Methods:
- Male and female mice were treated with corticosterone or a synthetic glucocorticoid.
- Grip strength and muscle mass were measured.
- Transcriptional responses in skeletal muscle were analyzed.
- Chemically-castrated male mice were used to assess androgen influence.
Main Results:
- Corticosterone reduced grip strength in females only, but decreased muscle mass in both sexes.
- Skeletal muscle transcriptional changes were more significant in males after corticosterone treatment.
- Synthetic glucocorticoids reduced grip strength in both sexes; females showed greater muscle atrophy.
- Androgen signaling partially influenced sex differences but did not fully explain the observed effects.
Conclusions:
- Sex differences exist in glucocorticoid-induced muscle atrophy and transcriptional responses.
- Androgen signaling contributes to, but does not entirely account for, these sex-specific effects.
- Further research is needed to fully elucidate the mechanisms behind sex differences in glucocorticoid action on skeletal muscle.
