Melatonin is as Effective as Testosterone in the Prevention of Soleus Muscle Atrophy Induced by Castration in Rats

Abstract

The purpose of this experiment was to compare the weight, insulinlike growth factor-I (IGF-I) expression, and ultrastructure of the soleus muscle in growing castrated rats treated with testosterone or melatonin. In this study, adult male Wistar albino rats were used. The groups were arranged as sham, castrated, and testosterone-or melatonin-injected groups after castration. The soleus muscle samples were fixed in Bouin's solution for immunohistochemistry, and in 2.5% gluteraldehyde in 0.1 M phosphate buffer (pH 7.4). Whereas castration reduced the soleus weight and fiber diameter, testosterone and melatonin administration increased them. IGF-I immunostaining observed in the satellite cells and periphery of the myofibers was least intense in the castrated group. Strong staining of IGF-I was observed in the testosterone-and melatonin-administered groups. The ultrastructure of the soleus muscle in castrated animals showed the important ultrastructural modifications related to degeneration. In these groups, degenerative mitochondria, glycogen clusters under the sarcolemma, irregular Z lines, and loss of lamina externa were observed. The ultrastructure of myofibrils in the testosterone-and melatonin-injected groups was similar to that in sham groups in view of structure. In conclusion, we suggest that melatonin is as effective as testosterone in the prevention of atrophy induced by castration through the IGF-I axis.

Targeting muscle signaling pathways to minimize adverse effects of androgen deprivation

“…In rodents, castration has been shown to result in a decreased myofiber cross-sectional area (CSA) in both type I and II fibers, which is consistent with the opposing effects seen with testosterone replacement (Oner et al 2008, White et al 2013, Rana et al 2014a). Decreased contractile strength (i.e., measured by twitch force in mice) has also been variably demonstrated (White et al 2013, De Naeyer et al 2014.…”

“…Mitochondrial structural changes (i.e., dissolved cristae) and swelling have also been observed (Boissonneault 2001, Oner et al 2008, Sinha et al 2014.…”

“…Experimental androgen deprivation using either of these models typically results in a rapid loss of muscle mass and increased fat stores (Oner et al 2008, White et al 2013, De Naeyer et al 2014.…”

“…Decreased contractile strength (i.e., measured by twitch force in mice) has also been variably demonstrated (White et al 2013, De Naeyer et al 2014. Furthermore, these studies have typically shown a rapid reversal of the castrationinduced changes following the administration of exogenous testosterone, giving further weight to the causal relationship between androgen deprivation and muscle atrophy (Oner et al 2008, Serra et al 2013a, De Naeyer et al 2014.…”

“…In addition, changes in morphology have been noted, such as irregular Z lines, loss of the lamina externa and glycogen clusters under the sarcomeres in androgendeprived rats (Sinha-Hikim et al 2006, Oner et al 2008, White et al 2013). Mitochondrial structural changes (i.e., dissolved cristae) and swelling have also been observed (Boissonneault 2001, Oner et al 2008, Sinha et al 2014.…”