Muscle-derived myostatin is a major endocrine driver of follicle-stimulating hormone synthesis
Luisina Ongaro 1, Xiang Zhou 1, Ying Wang 1, Hailey Schultz 2, Ziyue Zhou 1, Evan R S Buddle 1, Emilie Brûlé 2, Yeu-Farn Lin 1, Gauthier Schang 1, Adam Hagg 3, Roselyne Castonguay 4, Yewei Liu 5, Gloria H Su 6, Nabil G Seidah 7, Kevin C Ray 8, Seth J Karp 8, Ulrich Boehm 9, Frederique Ruf-Zamojski 10, Stuart C Sealfon 11, Kelly L Walton 3, Se-Jin Lee 5 12, Daniel J Bernard 1 2
Abstract
Myostatin is a paracrine myokine that regulates muscle mass in a variety of species, including humans. In this work, we report a functional role for myostatin as an endocrine hormone that directly promotes pituitary follicle-stimulating hormone (FSH) synthesis and thereby ovarian function in mice. Previously, this FSH-stimulating role was attributed to other members of the transforming growth factor-β family, the activins. Our results both challenge activin's eponymous role in FSH synthesis and establish an unexpected endocrine axis between skeletal muscle and the pituitary gland. Our data also suggest that efforts to antagonize myostatin to increase muscle mass may have unintended consequences on fertility.