Skeletal muscle-derived myostatin is a major endocrine driver of follicle-stimulating hormone synthesis

Myostatin is a paracrine myokine that regulates muscle mass in a variety of species, including humans. Here, we report a functional role for myostatin as an endocrine hormone directly promoting pituitary follicle-stimulating hormone (FSH) synthesis and thereby ovarian function. Previously, this FSH-stimulating role was attributed to other members of the transforming growth factor β family, the activins. The results both challenge activin’s eponymous role in FSH synthesis and establish an endocrine axis between skeletal muscle and the pituitary gland. The data also suggest that efforts to antagonize myostatin to treat muscle wasting disorders or lean mass loss in individuals treated with GLP-1 receptor agonists may have unintended consequences on fertility.