Modulation of mitochondrial gene expression by testosterone in skeletal muscle

Abstract

Testosterone plays a crucial role in determining the body composition of male mammals, includinghumans, due to its effects on muscle and fat mass. Age-related declines in serum testosterone levels in men have been linked to loss of skeletal muscle mass and strength, and physical performance [1-4]. This physical disorder, also known as sarcopenia, is a prevalent condition among the elderly, related to skeletal muscle dysfunction and cell apoptosis. Although the exact mechanisms underlying muscle loss with aging are not fully understood, accumulating evidence postulates that accelerated muscle cell apoptosis may play a central mechanism responsible for impairment of muscle performance [5,6]. Our previous research has shown that testosterone protects against oxidative stress H2O2-induced apoptosis in the C2C12 skeletal muscle cells at multiple levels, encompassing morphological, physiological, and biochemical aspects [7-9], playing the androgen receptor (AR) an active role in these events. Moreover, biochemical and mmunological data provided by our laboratory has supported the nonclassical localization of the R in mitochondria and microsomes of C2C12 skeletal muscle cells [10], from where it could be participating in the antiapoptotic effect of testosterone on skeletal muscle [8]. Thus, non-classical localization of AR from where it can exert non-genomic actions could be possible.