Muscle-derived myostatin is a major endocrine driver of follicle-stimulating hormone synthesis.

Summary

Using mouse models, the authors demonstrate that myostatin functions as an endocrine hormone that directly stimulates pituitary FSH synthesis, redefining the regulatory hierarchy for FSH beyond activins. This uncovers a skeletal muscle–pituitary endocrine axis and raises caution that myostatin antagonism to enhance muscle mass may adversely affect fertility.

Key Findings

• Myostatin acts systemically as an endocrine hormone to directly promote pituitary FSH synthesis in mice.
• The study challenges the prevailing view that activins are the primary FSH-stimulating ligands.
• An unexpected skeletal muscle–pituitary endocrine axis is established.
• Therapeutic antagonism of myostatin to increase muscle mass may have unintended fertility consequences.

Clinical Implications

Anti-myostatin therapies under development for sarcopenia or muscular dystrophy may carry fertility risks; reproductive monitoring or tailored dosing may be necessary. The findings also suggest potential avenues to modulate FSH in reproductive disorders.

Limitations

• Findings are in mice; human translational relevance and quantitative effect sizes are not provided in the abstract.
• Downstream signaling mechanisms and fertility outcomes under myostatin antagonism require further elucidation.

Future Directions

Validate the myostatin–FSH axis in humans; quantify reproductive outcomes with anti-myostatin therapies; dissect pituitary receptor/signaling pathways to enable targeted modulation without fertility trade-offs.