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.

OVX accompanied by mechanical unloading results in more rapid and severe bone loss than either OVX or unloading alone and therefore is associated with a greater likelihood of osteoporosis.

The aim of this study was to examine the longer-term effects of reduced gonadal hormones on food intake, food efficiency, voluntary running activity and body weight in mature male and female rats, compared to age-matched controls. We hypothesized that hormonal effects would differ for rats that were not rapidly growing and our results are consistent with this hypothesis. 6-8 month male and female rats were divided into four groups: Female and male control groups and a female and male experimental group. Control groups were intact for 46 weeks. Experimental groups were intact during Phase I (16 weeks), ovariectomized or orchidectomized during Phase II (20 weeks), and received estrogen or testosterone hormone replacement therapy (HRT) during the final Phase III (10 weeks). Food intake and running distance were monitored daily and body weight was recorded weekly for 46 weeks. Contrary to findings for young and growing animals, we did not observe a (1) stabilization of food intake in female rats following OVX, (2) loss of body weight with ORX in males, or (3) complete restoration of running activity in ORX males given testosterone, compared to females given estrogen. Feeding efficiency was not affected by aging in females or males. Loss of estrogen increased energy intake whereas reduced testosterone in males resulted in a negative energy balance. Findings suggest variable hormonal effects for aging male/female rats.

To determine rehabilitation exercise program effects under hormone deficient (ovariectomy or OVX) and hormone supplemented [OVX + 17-beta estradiol (E2)] conditions. Mature female rats (n = 123) were assigned to OVX or OVX + E2-supplemented groups. OVX and OVX + E2 groups were allocated to one of four conditions: (1) control, (2) hindlimb unweighted (HLU) for 4 weeks to induce muscle atrophy, (3) cage Recovery for 2 weeks after HLU, and (4) Recovery with 2 weeks of rehabilitation exercise program after 4 weeks of HLU. Atrophy following HLU was comparable for OVX and OVX + E2-supplemented rats and was significant in all muscles examined (soleus, tibialis anterior, plantaris, gastrocnemius, quadriceps). Also significant with HLU was the decline in muscle force (P < 0.05) in soleus, plantaris, gastrocnemius and tibialis anterior (quadriceps not tested). There were trends toward return of muscle mass in Recovery OVX and Recovery OVX + E2 groups but only the E2 supplemented OVX rats had return of muscle mass (4/5 muscles studied) with exercise. Peak tetanic tension (Po) returned to control values in the E2 supplemented Exercise rats but not in the unsupplemented Exercise group. For example, gastrocnemius Po for OVX HLU, OVX Recovery and OVX-Exercise groups was 82%*, 82%* and 76%* of control. Gastrocnemius Po for E2 supplemented HLU, Recovery and Exercise groups was 72%*, 95% and 106% of control (*P < 0.05 compared to control). H&E cross-sections from OVX-Exercise rats showed central nuclei. In conclusion, a rehabilitation exercise program to remediate acute atrophy in females appears more effective if E2 is present.

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