Myostatin in the pituitary-muscle axis: Roles in health and disease.

Myostatin (GDF-8), a TGF-β family myokine, regulates skeletal muscle growth and systemic metabolism and influences pituitary development and hormone secretion. This review summarizes experimental, translational, and clinical data linking myostatin to pituitary biology, including recent mouse evidence identifying muscle-derived myostatin as an endocrine driver of FSH synthesis via activin-type II/TGFBR1 signaling, with human confirmation pending. We analyze how pituitary disorders - growth hormone deficiency, acromegaly, hypercortisolism, central thyroid disease, central hypogonadism, and hypopituitarism - modify myostatin signaling, contributing to sarcopenia, anabolic resistance, and metabolic dysfunction. Across these conditions, human evidence remains limited and confounded by assay heterogeneity and comorbidities, as circulating myostatin often fails to mirror intramuscular changes. We propose an evidence framework emphasizing standardized assays (mature vs latent forms), longitudinal clinical cohorts, and integration of hormonal and functional endpoints. Myostatin remains a promising yet unvalidated biomarker and therapeutic target in endocrine-related muscle disease.