The impact of ovarian hormones on skeletal muscle plasticity has not been well established. We have preliminary data to suggest that the depletion of ovarian hormones due to ovariectomy attenuates the recovery of soleus skeletal muscle mass from hindlimb suspension disuse atrophy. Two studies were designed to determine the possible mechanisms of this effect. In study one, intact (Intact), ovariectomized (OVX), and ovariectomized with estrogen replacement female rats were randomly assigned to hindlimb suspension (10-days) and suspension with recovery (7-, 14-, or 28-days reloading normal ambulation). OVX altered the recovery of components of muscle mass, including myofiber hypertrophy, non-contractile tissue expansion, and myofiber regeneration after 7- and 14-days of reloading recovery. Muscle recovery was delayed, but not ablated, as components of muscle mass were restored after 28-days of recovery in OVX animals. Estrogen was determined essential for reloading recovery, as replacement prior to or after atrophy resulted in muscle recovery by day 14 of reload. In study two, initial myofiber damage and inflammatory processes during the initial week of recovery were studied in intact, OVX, and estrogen replacement animals. The initial 3-days of recovery were the critical period of estrogen action on recovery. Circulating creatine kinase and myofiber membrane dystrophin disruption markers of damage were not altered by ovarian hormone depletion during recovery. Leukocyte infiltration in recovering muscle increased and was prolonged in OVX soleus as compared with Intact. Mast cell concentration was increased by ovariectomy treatment and decreased by estrogen administration. The temporal induction of macrophages in recovering muscle, however, was not altered during recovery. The temporal induction of cyclooxygenase-2 (COX-2) and the pro-inflammatory cytokines IL-1beta and IL-6 mRNA abundances were similar regardless of ovarian hormone status. Taken together, these studies suggest that estrogen is critical for efficient recovery of muscle from atrophy, and may be partially explained by its' effects on leukocyte infiltration during reloading. This understanding the importance of estrogen on muscle growth processes during reloading after atrophy progresses therapeutic treatments targeted at the maintenance and recovery of muscle mass.
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