Androgens and skeletal muscle: cellular and molecular action mechanisms underlying the anabolic actions

Abstract

Androgens increase both the size and strength of skeletal muscle via diverse mechanisms. The aim of this review is to discuss the different cellular targets of androgens in skeletal muscle as well as the respective androgen actions in these cells leading to changes in proliferation, myogenic differentiation, and protein metabolism. Androgens bind and activate a specific nuclear receptor which will directly affect the transcription of target genes. These genes encode muscle-specific transcription factors, enzymes, structural proteins, as well as microRNAs. In addition, anabolic action of androgens is partly established through crosstalk with other signaling molecules such as Akt, myostatin, IGF-I, and Notch. Finally, androgens may also exert non-genomic effects in muscle by increasing Ca(2+) uptake and modulating kinase activities. In conclusion, the anabolic effect of androgens on skeletal muscle is not only explained by activation of the myocyte androgen receptor but is also the combined result of many genomic and non-genomic actions.

Effects of immunocastration on growth performance, body composition, meat quality, and boar taint

“…Gispert et al (2010) reported that meat from CM reached the greatest extent of IMF, boars showed the least, and gilts and CM were in between. Dubois et al (2012) came to the conclusion that boars have lower proportion of fat and therefore also a lesser extent of IMF due to the anabolic effects of androgynous steroids, such as testosterone. This can cause problems, as even in CM the IMF in some muscles is less than the 2-3% which is recommended for optimal sensory quality.…”

Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone

“…This suggests that other factors, which are not corrected by testosterone therapy, may play a greater role for the decreased insulin sensitivity and reduced oxidative capacity in these male individuals. Androgen mediates many of its actions in skeletal muscle by binding and activating its receptor, the androgen receptor (AR), which leads to transcription of target genes (3). A recent study of myotubes from male donors has shown that the testosterone-mediated increase in palmitate oxidation was attenuated in the presence of an AR antagonist (24).…”

“…Consistently, other studies have reported that testosterone therapy stimulates lipid oxidation in hypopituitary men (20,21), and that testosterone deficiency, induced by a gonadotropin-releasing hormone analog in younger men, increases adiposity and decreases fat oxidation and resting energy expenditure (22). The possible effect of testosterone on energy metabolism is supported by a recent microarray study of orchidectomized mice, in which testosterone replacement in addition to the known positive effects on muscle mass and insulin-like growth factor 1/Akt signaling also normalized the expression of OxPhos genes (3,23). Finally, a recent study of myotubes from male donors has shown that a testosterone-induced increase in palmitate oxidation was associated with increased activation of AMP-activated protein kinase (AMPK) and p38 MAPK (24), which are known regulators of mitochondrial biogenesis (25).…”

Targeting muscle signaling pathways to minimize adverse effects of androgen deprivation

“…Due to the important role of androgen-receptor signaling in the development of prostate cancer, androgen deprivation therapy (ADT) is commonly used for both locally advanced and metastatic disease; however, benefits are accompanied by a variety of side effects due to the widespread expression of sex steroid receptors (Basaria & Bhasin 2012, Cheung et al 2014. Adverse effects include loss of muscle, accelerated bone loss and increased adiposity as well as anemia, hot flushes and sexual dysfunction (Basaria & Bhasin 2012, Dubois et al 2012, Chang et al 2013, Grossmann et al 2013, Serra et al 2013a, White et al 2013. Consequently, ADT is associated with increased morbidity, frailty and reduced quality of life (Alibhai et al 2010).…”

“…Testosterone and perhaps its derivative estradiol are among the key mediators in these processes; however, the specific mechanisms and interactions are not fully elucidated (Wu & von Eckardstein 2003, Finkelstein et al 2013. Testosterone administration has a consistent, dose-dependent anabolic effect in a number of populations, including androgen-deficient and eugonadal young men, older men and men with chronic diseases such as HIV (Herbst & Bhasin 2004, Sinha-Hikim et al 2006, Miller 2009, Jones et al 2010, Dubois et al 2012, Jasuja et al 2014. However, benefits of testosterone supplementation on physical function and subsequent quality of life are more difficult to define, despite being the most relevant factor for the patient (Herbst & Bhasin 2004, Cheung et al 2014.…”