Sex Differences in Human Myogenesis Following Testosterone Exposure.

Area of Science:

• Cell Biology
• Endocrinology
• Muscle Physiology

Background:

• Previous studies noted sex-specific differences in muscle cells concerning sex hormones and steroidogenesis.
• Androgen exposure's impact on intracellular myogenesis and regeneration pathways requires further elucidation.

Purpose of the Study:

• To investigate sex-related differences in intracellular processes of myogenesis and regeneration in human skeletal muscle cells following testosterone exposure.
• To analyze molecular pathways and myokine release in response to varying testosterone doses in 46XX and 46XY cells.

Main Methods:

• Primary neonatal 46XX and 46XY human skeletal muscle cells were treated with escalating testosterone concentrations (0.5–100 nM) for 24 hours.
• Western blot, real-time PCR, and Luminex assays were employed to assess gene/protein expression and myokine release.
• Statistical analysis included unpaired Student's t-test and one-way ANOVA for repeated measures.

Main Results:

• 46XX cells exhibited increased MYF6, IGF-I, IGF-II, and CXCL1, with decreased GM-CSF, IL-9, and IL-12 expression/release.
• Testosterone upregulated GM-CSF and CXCL1 in 46XY cells, with no significant changes in other analyzed myokines.
• MAPK pathway activation was preferential in 46XX cells, while PI3K/AKT pathway activation was preferential in 46XY cells.

Conclusions:

• Androgen exposure elicits distinct intracellular responses in 46XX and 46XY muscle cells.
• These sex-specific responses lead to differential activation of muscle cell growth and energy metabolic pathways.
• Findings highlight the importance of considering sex in understanding muscle development and response to hormonal stimuli.