摘要：SummaryAndrogens have a robust effect on skeletal muscles to increase muscle mass and strength. The molecular mechanism of androgen/androgen receptor (AR) action on muscle strength is still not well known, especially for the regulation of sarcomeric genes. In this study, we generated androgen-induced hypertrophic model mice, myofiber-specific androgen receptor knockout (cARKO) mice supplemented with dihydrotestosterone (DHT). DHT treatment increased grip strength in control mice but not in cARKO mice. Transcriptome analysis by RNA-seq, using skeletal muscles obtained from control and cARKO mice treated with or without DHT, identified a fast-type muscle-specific novel splicing variant ofMyosin light-chain kinase 4 (Mylk4)as a target of AR in skeletal muscles.Mylk4knockout mice exhibited decreased maximum isometric torque of plantar flexion and passive stiffness of myofibers due to reduced phosphorylation of Myomesin 1 protein. This study suggests that androgen-induced skeletal muscle strength is mediated with Mylk4 and Myomesin 1 axis.Graphical abstractDisplay OmittedHighlights•DHT increases muscle strength through myofiber AR•Myofiber AR increases a fast-type muscle-specific novel splicing variant ofMylk4•MYLK4 regulates muscle strength and muscle stiffness•MYLK4 induces phosphorylation of MYOM1Animal Physiology; Molecular Physiology; Molecular Biology; Endocrinology
