Ovariectomy prevents the recovery of atrophied gastrocnemius skeletal muscle mass

Abstract

The recovery of atrophied muscle mass in animals is thought to be dependent on a number of factors including hormones, cytokines, and/or growth factor expression. The Akt/mammalian target of rapamycin (mTOR) signaling pathway is believed to be activated by these various factors, resulting in skeletal muscle growth through the initiation of protein synthesis. It was hypothesized that surgical removal of the ovaries (Ovx) may alter activation of the Akt/mTOR signaling pathway, a mechanism necessary for muscle regrowth. To test this, 36 Sprague-Dawley rats underwent Ovx or sham surgeries. A portion of the animals were then subjected to hindlimb unloading (HLU) for 28 days. After HLU, one group of Sham and Ovx rats underwent a 14-day recovery period in which the animals were allowed free cage ambulation. The HLU animals demonstrated approximately 21-27% reduction in medial gastrocnemius muscle mass irrespective of whether the ovaries were intact or not. The Sham animals that were reloaded recovered their atrophied muscle mass; however, the Ovx group failed to recover any of the atrophied muscle mass with reloading. The failure to recover muscle mass in the Ovx group was associated with reduced phosphorylation levels of both Akt and p70s6k, whereas in the Sham recovery animals no reductions were found in Akt phosphorylation and significant increases in p70s6k activation were detected. Finally, no differences were detected in mTOR phosphorylation in any of Sham or Ovx groups. These results suggest that ovariectomy surgeries could be detrimental to the recovery of atrophied muscle mass.

Determinants of Disuse-Induced Skeletal Muscle Atrophy: Exercise and Nutrition Countermeasures to Prevent Protein Loss

“…In addition, most of the genes downregulated and several genes upregulated during unloading return to basal levels within a few hours of recovery (78). These effects result in relatively rapid recovery of the fiber cross-sectional area (135,138) and muscle mass (15,(136)(137)(138)(139)(140)(141).…”

“…In addition, others have demonstrated that the downstream pathway of Akt, including ribosomal protein S6, is activated early in recovery from disuse muscle (soleus) atrophy, suggesting that the recovery of atrophied muscles is facilitated by increased mRNA translation during the early stages of resumption of loading (140). Moreover, another study concluded that a 2-wk recovery period from nonweight bearing significantly increases the activation levels of S6K and ribosomal protein S6 in medial gastrocnemius muscles of sham-operated (ovariectomy) rats, but does not influence appreciably the levels of phosphorylated Akt or mTOR in the same animals (141). Concerning these contradictory outcomes, our opinion is that different regulation feedbacks detected for different muscles during unloading (82) and greatly variable time-course regulatory responses of protein translation factors during reloading (139) should be carefully considered when analyzing the effects of disuse and recovery, respectively.…”

Estrogens maintain skeletal muscle and satellite cell functions

“…Although the effects of androgens on muscle function have been evaluated extensively, the roles of estrogens in muscle have been largely unknown. Recent studies have revealed that the levels of estrogens are associated with muscle mass (McClung et al 2006, Sitnick et al 2006, Sugiura et al 2006, Pollanen et al 2011. Ovariectomized (OVX) mice fail to fully recover muscle mass after hindlimb suspension-induced muscle atrophy followed by reloading (McClung et al 2006).…”

Effect of daidzein, 4-methylbenzylidene camphor or estrogen on gastrocnemius muscle of osteoporotic rats undergoing tibia healing period

“…Bone healing period is associated with an inactivity of the muscles that may cause their atrophy (Machida & Booth 2004). It was demonstrated that ovarian hormone deficiency could play a role in the failure to recover muscle mass after a period of inactivity of the muscle (Sitnick et al 2006). The presence of estrogen receptors in skeletal muscle indicates that skeletal muscle function is also regulated by estrogen (Piccone et al 2004).…”