Androgens negatively regulate myostatin expression in an androgen-dependent skeletal muscle

Myostatin is an important negative regulator of skeletal muscle growth, while androgens are strong positive effectors. In order to investigate the possible interaction between myostatin and androgen pathways, we followed myostatin expression in the androgen-dependent levator ani (LA) muscle of the rat as a function of androgen status. By testosterone deprivation (castration), we induced LA growth arrest in young male rats, whilst atrophy in adult ones, however, both processes could be reversed by testosterone supplementation. After castration, a significant up-regulation of active myostatin protein (and its propeptide) was found, whereas the subsequent testosterone treatment reduced myostatin protein levels to normal values in both young and adult rats. Similarly, a testosterone-induced suppression of myostatin mRNA levels was observed in castrated adult but not in young animals. Altogether, androgens seem to have strong negative impact on myostatin expression, which might be a key factor in the weight regulation of LA muscle. (C) 2007 Elsevier Inc. All rights reserved.