Beyond its Psychiatric Use: The Benefits of Low-dose Lithium Supplementation.

Lithium is most well-known for its mood-stabilizing effects in the treatment of bipolar disorder. Due to its narrow therapeutic window (0.5-1.2 mM serum concentration), there is a stigma associated with lithium treatment and the adverse effects that can occur at therapeutic doses. However, several studies have indicated that doses of lithium under the predetermined therapeutic dose used in bipolar disorder treatment may have beneficial effects not only in the brain but across the body. Currently, literature shows that low-dose lithium (≤0.5 mM) may be beneficial for cardiovascular, musculoskeletal, metabolic, and cognitive function, as well as inflammatory and antioxidant processes of the aging body. There is also some evidence of low-dose lithium exerting a similar and sometimes synergistic effect on these systems. This review summarizes these findings with a focus on low-dose lithium's potential benefits on the aging process and age-related diseases of these systems, such as cardiovascular disease, osteoporosis, sarcopenia, obesity and type 2 diabetes, Alzheimer's disease, and the chronic low-grade inflammatory state known as inflammaging. Although lithium's actions have been widely studied in the brain, the study of the potential benefits of lithium, particularly at a low dose, is still relatively novel. Therefore, this review aims to provide possible mechanistic insights for future research in this field.

Mechanisms of Estrogen Influence on Skeletal Muscle: Mass, Regeneration, and Mitochondrial Function.

Human menopause is widely associated with impaired skeletal muscle quality and significant metabolic dysfunction. These observations pose significant challenges to the quality of life and mobility of the aging population, and are of relevance when considering the significantly greater losses in muscle mass and force-generating capacity of muscle from post-menopausal females relative to age-matched males. In this regard, the influence of estrogen on skeletal muscle has become evident across human, animal, and cell-based studies. Beneficial effects of estrogen have become apparent in mitigation of muscle injury and enhanced post-damage repair via various mechanisms, including prophylactic effects on muscle satellite cell number and function, as well as membrane stability and potential antioxidant influences following injury, exercise, and/or mitochondrial stress. In addition to estrogen replacement in otherwise deficient states, exercise has been found to serve as a means of augmenting and/or mimicking the effects of estrogen on skeletal muscle function in recent literature. Detailed mechanisms behind the estrogenic effect on muscle mass, strength, as well as the injury response are beginning to be elucidated and point to estrogen-mediated molecular cross talk amongst signalling pathways, such as apoptotic signaling, contractile protein modifications, including myosin regulatory light chain phosphorylation, and the maintenance of muscle satellite cells. This review discusses current understandings and highlights new insights regarding the role of estrogen in skeletal muscle, with particular regard to muscle mass, mitochondrial function, the response to muscle damage, and the potential implications for human physiology and mobility.

Osteokines and Bone Markers at Rest and following Plyometric Exercise in Pre- and Postmenopausal Women.

The effect of plyometric exercise on bone biomarkers has been studied in pediatric and young adult populations in order to better understand how exercise influences bone homeostasis. However, there are no such data in postmenopausal women, a group characterized by an uncoupling of the bone resorption-formation cycle. This study examined the serum concentrations of sclerostin, dickkopf-1 (DKK1), c-terminal crosslinking telopeptides of type I collagen (CTXI), and procollagen type I amino-terminal propeptide (PINP) at rest and following a single bout of plyometric exercise in 20 premenopausal (23.1 ± 2.3 years) and 20 postmenopausal women (57.9 ± 4.3 years). The exercise consisted of 128 jumps, organized into 5 circuit stations. Blood samples were obtained prior to and 5 min, 1 h, and 24 h postexercise. At rest, postmenopausal women had significantly higher sclerostin and CTXI, but lower DKK1 than premenopausal women. Sclerostin increased 5 min postexercise only in the premenopausal group. DKK1 decreased 24 h postexercise in the premenopausal women while it decreased 1 h postexercise in the postmenopausal women. In both groups, CTXI did not change across time and PINP decreased 5 min and 1 h postexercise (p < 0.05). The PINP/CTXI ratio decreased 5 min and 1 h postexercise then significantly increased 24 h postexercise only in premenopausal women. These results indicate that although plyometric exercise is effective in eliciting osteoanabolic effects in younger women; such an effect is not evident in postmenopausal women.

Lack of influence of estrogen on myosin phosphorylation and post-tetanic potentiation in muscles from young adult C57BL mice.

Estrogen influences myosin phosphorylation and post-tetanic potentiation in murine fast muscle. We tested the hypothesis that this influence is mediated by estrogen effects on skeletal myosin light chain kinase (skMLCK) activity. To this end, extensor digitorum longus muscles from female wildtype and skMLCK-absent (skMLCK-/-) mice were grouped as follows: ovariectomized with estrogen (E+), ovariectomized without estrogen (E-), sham surgery, and intact baseline. At 8 weeks of age, the ovariectomized groups were ovariectomized followed by implantation of either a 0.1 mg 17ß-estradiol (E+) or placebo pellet (E-). Two weeks later, muscles were isolated and suspended in vitro (25° C) for determination of regulatory light chain phosphorylation and post-tetanic potentiation. Regulatory light chain phosphorylation was not different across conditions within either genotype although wildtype values were significantly greater than skMLCK-/- values. Consistent with this, the potentiation of concentric twitch force was similar between E+ and E- groups within each genotype but wildtype values were greater than skMLCK-/- values. However, unaltered estradiol levels following ovariectomy, likely due to previously underappreciated confounds of mouse age, development, and growth during estrogen supplementation, prevented direct testing of the hypothesis. Future studies should note the importance of estrous cycles and continuing physiological developments of young adult mice when working with ovarian hormones.

Delay in post-ovariectomy estrogen replacement negates estrogen-induced augmentation of post-exercise muscle satellite cell proliferation.

This study examined the effects of a delay in post-ovariectomy replacement of 17ß-estradiol (estrogen) on the post-exercise proliferation of muscle satellite cells. Nine-week-old, ovariectomized, female Sprague-Dawley rats (n = 64) were distributed among 8 groups based on estrogen status (0.25 mg estrogen pellet or sham), exercise status (90 min run at 17 m·min(-1) and a grade of -13.5° or unexercised), and estrogen replacement ("proximal", estrogen replacement within 2 weeks; or "delayed", estrogen replacement at 11 weeks following ovariectomy). Significant increases in satellite cells were found in the soleus and white gastrocnemius muscle (immunofluorescent colocalization of nuclei with Pax7) 72 h following eccentric exercise (p < 0.05) in all exercised groups. Proximal E2 replacement resulted in a further augmentation of muscle satellite cells in exercised rats (p < 0.05) relative to the delayed estrogen replacement group. Expression of PI3K was unaltered and phosphorylation of Akt relative to total Akt increased following estrogen supplementation and exercise. Exercise alone did not alter the expression levels of Akt. An 11 week delay in post-ovariectomy estrogen replacement negated the augmenting influence seen with proximal (2 week delay) post-ovariectomy estrogen replacement on post-exercise muscle satellite cell proliferation. This effect appears to be independent of the PI3K-Akt signaling pathway.

Alternative treatments for muscle injury: massage, cryotherapy, and hyperbaric oxygen.

Current evidence suggests that popular alternative therapies such as massage, cryotherapy, and hyperbaric oxygen exposure as currently practiced on humans have little effect on recovery from minor muscle damage such as induced by exercise. While further research is still needed, hyperbaric oxygen exposure shows clear promise for potentially being a successful adjunct treatment for enhancing muscle repair and recovery from more severe crush on contusion injury in humans. Cryotherapy or icing, as currently practiced, will not likely be successful in cooling muscle sufficiently to have any significant influence on muscle repair regardless of the degree of injury. However, based on studies in animal models, it may be that if sufficient muscle cooling could be achieved in humans, it could actually delay recovery and increase muscle scarring following significant muscle damage. Conclusions about the effectiveness of massage on influencing muscle recovery from more severe injury cannot yet be made due to a lack of experimental evidence with a more significant muscle damage model.

Is intramuscular pressure a valid diagnostic criterion for chronic exertional compartment syndrome?

OBJECTIVE: To compare the intramuscular pressure (IMP) of the tibialis anterior in healthy persons under several exercise conditions with the IMP diagnostic criteria in use for diagnosing chronic exertional compartment syndrome (CECS). DATA SOURCES: A search of MEDLINE for the period 1966 to March 2010 used the words "intramuscular," "intracompartment," "anterior compartment," and "anterior tibial compartment" linked with "pressure." Reference lists of relevant studies were searched for further articles. STUDY SELECTION: Articles published in English that tested IMP in the tibialis anterior in asymptomatic humans were included if they used no interventions before or during IMP testing. Studies were excluded if data were given as a percentage of IMP or if the data could not be extracted for the tibialis anterior compartment alone. From 515 articles identified, 38 studies met selection criteria DATA EXTRACTION: : Details of the studies included IMP measurement technique, timing of measurement (before, during, and/or after exercise), type and duration of exercise, the number of compartments measured, and participants' ages. Mean or median pressure was recorded in mm Hg. DIAGNOSTIC STANDARD: Criteria for the upper limit of normal pressure under different conditions were the Pedowitz criterion for preexercise IMP (15 mm Hg), the Puranen criterion for IMP during exercise (50 mm Hg), the Styf criterion for relaxation pressure (30-55 mm Hg), and the Pedowitz criteria for mean 1-minute postexercise and 5-minutes postexercise pressures (30 mm Hg and 50 mm Hg, respectively). MAIN RESULTS: Exercise was mostly treadmill walking/running (duration, 1.5-120 min) or ankle dorsiflexion (duration, 10 sec-20 min). Methods of measuring IMP varied from study to study. The lowest mean IMP was identified preexercise at rest (range, 0-20 mm Hg). Five of the 34 studies found a higher mean resting pressure than the criterion (15 mm Hg). Mean pressure during exercise (10 studies, 9 of running, with durations of 5-20 min) varied between 23 mm Hg and 66 mm Hg. Two of these studies found a higher mean peak pressure during exercise than the criterion (50 mm Hg). Mean relaxation IMP, measured in 9 studies, was approximately 25 mm Hg in the 1 treadmill study in which it was measured, whereas studies of dorsiflexion found a range of approximately 5 to 15 mm Hg. All the studies found lower mean relaxation IMP than the criterion (35-50 mm Hg). One of 11 studies and 1 of 10 studies found the mean postexercise IMP after 1 minute and 5 minutes to be above the criteria of 30 mm Hg and 20 mm Hg, respectively. CONCLUSIONS: The limits of anterior tibialis IMP before, during, and after exercise that are used as diagnostic criteria for CECS would include many asymptomatic persons. Intramuscular pressure values were not valid criteria for the presence of the syndrome.

The role of estrogen receptor-α in estrogen-mediated regulation of basal and exercise-induced Hsp70 and Hsp27 expression in rat soleus.

We examined the influence of estrogen receptor-alpha (ERα) activation on estrogen-mediated regulation of heat shock proteins 70 (Hsp70) and 27 (Hsp27) in soleus. Ovariectomized rats received estrogen (EST), an ERα agonist (propyl pyrazole triol, PPT), both (EST+PPT), or a sham, and they served as either unexercised controls or were subjected to exercise by having to run downhill (17 m/min, -13.5° grade) for 90 min. At 72 h postexercise, soleus muscles were removed and either immunohistochemically stained for Hsp70 and myosin heavy chain or homogenized for Western blotting for Hsp70 and Hsp27. Elevated (p < 0.05) basal Hsp70 in both type I and II fibres in the unexercised EST, PPT, and EST+PPT groups relative to unexercised sham animals was noted. Compared with Hsp70 levels in the unexercised animals, that in exercised animals was elevated (p < 0.05) in both sham and PPT groups but not in EST and EST+PPT groups. Western blot determined that Hsp27 levels were not significantly different between groups. Hence, the ability of estrogen to augment resting type I and type II muscle fibre Hsp70 content is primarily mediated via muscle ERα. However, the blunted Hsp70 response following damaging exercise in estrogen-supplemented animals does not appear to be fully accounted for by ERα-mediated effects.

Metabolic cost and mechanics of walking in women with fibromyalgia syndrome.

BACKGROUND: Fibromyalgia syndrome (FS) is characterized by the presence of widespread pain, fatigue, muscle weakness and reduced work capacity. Previous research has demonstrated that women with fibromyalgia have altered walking (gait) patterns, which may be a consequence of muscular pain. This altered gait is characterized by greater reliance on hip flexors rather than ankle plantar flexors and resembles gait patterns seen in normal individuals walking at higher speeds, suggesting that gait of individuals with fibromyalgia may be less efficient.This study compared rates of energy expenditure of 6 females with FS relative to 6 normal, age and weight matched controls, at various walking speeds on a motorized treadmill. Metabolic measurements including V02 (ml/kg/min), respirations, heart rate and calculated energy expenditures as well as the Borg Scale of Perceived Exertion scale ratings were determined at baseline and for 10 min while walking at each of 2, 4 and 5 km/hour on 1% grade. Kinematic recordings of limb and body movements while treadmill walking and separate measurements of ground reaction forces while walking over ground were also determined. In addition, all subjects completed the RAND 36-Item Health Survey (1.0). FINDINGS: Gait analysis results were similar to previous reports of altered gait patterns in FS females. Despite noticeable differences in gait patterns, no significant differences (p > 0.05) existed between the FS and control subjects on any metabolic measures at any walking speed. Total number of steps taken was also similar between groups. Ratings on the Borg Scale of Perceived Exertion, the RAND and self-reported levels of pain indicated significantly greater (p < 0.05) perceived effort and pain in FS subjects relative to control subjects during walking and daily activities. CONCLUSIONS: The altered gait patterns and greater perceptions of effort and pain did not significantly increase the metabolic costs of walking in women with FS and hence, increased sensations of fatigue in FS women may not be related to alteration in metabolic cost of ambulation.

Estrogen replacement and skeletal muscle: mechanisms and population health.

There is a growing body of information supporting the beneficial effects of estrogen and estrogen-based hormone therapy (HT) on maintenance and enhancement of muscle mass, strength, and connective tissue. These effects are also evident in enhanced recovery from muscle atrophy or damage and have significant implications particularly for the muscular health of postmenopausal women. Evidence suggests that HT will also help maintain or increase muscle mass, improve postatrophy muscle recovery, and enhance muscle strength in aged females. This is important because this population, in particular, is at risk for a rapid onset of frailty. The potential benefits of estrogen and HT relative to skeletal muscle function and composition combined with other health-related enhancements associated with reduced risk of cardiovascular events, overall mortality, and metabolic dysfunction, as well as enhanced cognition and bone health cumulate in a strong argument for more widespread and prolonged consideration of HT if started proximal to menopausal onset in most women. Earlier reports of increased health risks with HT use in postmenopausal women has led to a decline in HT use. However, recent reevaluation regarding the health effects of HT indicates a general lack of risks and a number of significant health benefits of HT use when initiated at the onset of menopause. Although further research is still needed to fully delineate its mechanisms of action, the general use of HT by postmenopausal women, to enhance muscle mass and strength, as well as overall health, with initiation soon after the onset of menopause should be considered.

Effect of creatine supplementation on muscle damage and repair following eccentrically-induced damage to the elbow flexor muscles.

We investigated effects of creatine (Cr) supplementation (CrS) on exercise-induced muscle damage. Untrained males and females (N = 27) ages 18-25, with no CrS history in the past 4 months, were randomly assigned to CrS (creatine and carbohydrate) (n = 9), placebo (P) (carbohydrate only) (n = 9), or control (C) (no supplements) groups (n = 9). Participants followed a 5-day Cr loading protocol of 40 g·day(-1), divided for 5 days prior to exercise, reduced to 10 g g·day(-1) for 5 days following exercise. Testing consisted of 5 maximal isometric contractions at 90 arm flexion with the preferred arm on a CYBEX NORM dynamometer, assessed prior to, immediately following, and 24, 48, 72, and 96 hours post muscle-damaging procedures. Damage was induced to the elbow flexor muscles using 6 sets of 10 eccentric contractions at 75 °/sec, 90 °/sec and 120 °/sec. Participants were asked to rate their muscle soreness on a scale of 1-10. Data was analyzed using repeated-measures ANOVA, with an alpha of 0.05. No significant differences were found between muscle force loss and rate of recovery or muscle soreness between groups over the 96 hr recovery period (p > 0.05). Across all 3 experimental groups an initial decrease in force was observed, followed by a gradual recovery. Significant differences were found between baseline and all others times (p = 0.031,0 .022, 0.012, 0.001 respectively), and between the 48 hour and 96 hour time periods (p = 0.034). A weak negative correlation between subjectively rated muscle soreness and mean peak isometric force loss (R(2) = 0.0374 at 96 hours), suggested that muscle soreness and muscle force loss may not be directly related. In conclusion, 5 days of Cr loading, followed by a Cr maintenance protocol did not reduce indices of muscle damage or speed recovery of upper body muscles following eccentrically induced muscle damage.

Effectiveness of regular proactive massage therapy for novice recreational runners.

OBJECTIVES: To assess effects of a regular massage program on novice runners over a longer-term training period. PARTICIPANTS: Twelve control and sixteen massage subjects took part in the study. SETTING: Both groups participated in 10-week running preparation clinics. DESIGN: An individualized massage treatment plan was developed for each massage group participant. Massage group subjects met weekly with a registered massage therapist for a half hour massage. Control subjects were given no massage treatments. MAIN OUTCOME MEASURES: All participants maintained a running journal that recorded running behavior: frequency, distance, intensity, and pain. At weeks 1, 5, and 10, muscle strength, leg pain, daily functioning, and running confidence were assessed. RESULTS: The running behavior of both groups was similar (p > 0.05). Both groups experienced a considerable amount of pain when they ran. However, 100% of the massage group compared to 58.3% of control group completed the 10 km race. CONCLUSIONS: A regular massage therapy program during training did not improve indices of muscle strength, pain perception, daily functioning or running confidence. However, the entire massage group met their targeted running goals while only half of the control was able to do so however this difference may not be attributable to the massage intervention.

Benefits of estrogen replacement for skeletal muscle mass and function in post-menopausal females: evidence from human and animal studies.

Age related loss of skeletal muscle mass and strength accelerates with the onset of menopause in women. Recent evidence from human and animal studies provides compelling evidence for the role of estrogen based hormone replacement therapy (HRT) in maintaining and enhancing muscle mass and strength and protecting against muscle damage. The physiological mechanisms by which estrogen can positively influence skeletal muscle mass and strength and protect against post-damage inflammation and disruption are also beginning to emerge. These less well known benefits of estrogen for skeletal muscle coupled with other benefits of estrogen to bone and metabolic health in older females provide further incentives for HRT use to enhance overall health in post-menopausal women. New research also attests to the safety of shorter term HRT in younger post-menopausal females. Overall the benefits of HRT to muscle health and function could assist in offsetting age related loss of muscle mass and function and delay age related morbidity and their use for overall health benefits in aging females should continue to be evaluated.

The influence of estrogen on skeletal muscle: sex matters.

As women enter menopause, the concentration of estrogen and other female hormones declines. This hormonal decrease has been associated with a number of negative outcomes, including a greater incidence of injury as well as a delay in recovery from these injuries. Over the past two decades, our understanding of the protective effects of estrogen against various types of injury and disease states has grown immensely. In skeletal muscle, studies with animals have demonstrated that sex and estrogen may potentially influence muscle contractile properties and attenuate indices of post-exercise muscle damage, including the release of creatine kinase into the bloodstream and activity of the intramuscular lysosomal acid hydrolase, beta-glucuronidase. Furthermore, numerous studies have revealed an estrogen-mediated attenuation of infiltration of inflammatory cells such as neutrophils and macrophages into the skeletal muscles of rats following exercise or injury. Estrogen has also been shown to play a significant role in stimulating muscle repair and regenerative processes, including the activation and proliferation of satellite cells. Although the mechanisms by which estrogen exerts its influence upon indices of skeletal muscle damage, inflammation and repair have not been fully elucidated, it is thought that estrogen may potentially exert its protective effects by: (i) acting as an antioxidant, thus limiting oxidative damage; (ii) acting as a membrane stabilizer by intercalating within membrane phospholipids; and (iii) binding to estrogen receptors, thus governing the regulation of a number of downstream genes and molecular targets. In contrast to animal studies, studies with humans have not as clearly delineated an effect of estrogen on muscle contractile function or on indices of post-exercise muscle damage and inflammation. These inconsistencies have been attributed to a number of factors, including age and fitness level of subjects, the type and intensity of exercise protocols, and a focus on sex differences that typically involve factors and hormones in addition to estrogen. In recent years, hormone replacement therapy (HRT) or estrogen combined with exercise have been proposed as potentially therapeutic agents for postmenopausal women, as these agents may potentially limit muscle damage and inflammation and stimulate repair in this population. While the benefits and potential health risks of long-term HRT use have been widely debated, controlled studies using short-term HRT or other estrogen agonists may provide future new and valuable insights into understanding the effects of estrogen on skeletal muscle, and greatly benefit the aging female population. Recent studies with older females have begun to demonstrate their benefits.

The effect of tapering period on plasma pro-inflammatory cytokine levels and performance in elite male cyclists.

The aim of this study was to investigate the effect of two different tapering period lengths on the concentration of plasma interleukin- 6 (IL-6), interleukin (IL-1ß) and tumor necrosis factor-α (TNF-α) and performance in elite male cyclists. To this end, after completing 8 weeks progressive endurance exercise, twenty four high-level endurance cyclists were randomly assigned to one of two groups: a control group of cyclists (n = 12) continued performing progressive weekly training volume for 3 weeks while a taper group of cyclists (n = 12) proceeded with a 50% reduction in weekly training volume relative to the control group. A simulated 40 min time trial (40TT) performance ride was used as the criterion index of performance before and after the tapering period to evaluate the physiological and performance effects of each protocol. Blood samples were collected immediately post-40TT from all participants at the beginning of week 1, and the end of weeks 4, 8, 9 and 11. IL-1ß, IL-6 and TNFα were assayed using a standard commercial ELISA kits (Quantikine; R & D Systems, Minneapolis, MN). The mean time to complete the 40TT in the taper group decreased significantly (p < 0.01) after both 1 and 3 weeks with reduced training volume relative to the control group. There were significant reductions in (p < 0.001) IL-1ß, IL-6 and TNFα concentrations in the taper group relative to the control group at the end of the 3 week tapering period, but not at the end of the 1 week tapering period. These results demonstrate that both a 1 and a 3 week taper period will result in improved physical performance in trained cyclists but only a 3 week taper period will result in attenuation of post-exercise pro- inflammatory cytokines when compared to those continuing a more intense training regimen. Key pointsThe excessive endurance exercise-induced elevations in pro-inflammatory cytokines would, in turn, stimulate the release of anti-inflammatory cytokines.Elevations in pro-inflammatory cytokines indicate athletes are highly susceptible to infections.1and 3-week taper periods will reduce circulating pro-inflammatory cytokine levels thereby possibly limiting the chances of infection and potentially reducing the effects of these cytokines in inducing fatigue-like symptoms in athletes.

Progesterone and estrogen influence postexercise leukocyte infiltration in overiectomized female rats.

Limited research has been conducted on the effects of progesterone alone, or in combination with estrogen, on leukocyte infiltration in skeletal muscle following exercise. To investigate the effects of these female sex hormones, ovariectomized female rats were divided into 4 exercise and 4 control groups: sham, estrogen, progesterone, and a combination of estrogen plus progesterone. Following 8 days of hormone replacement and 24 h postexercise, soleus (red) and superficial (white) vastus muscles were removed and immunostained for His48 (neutrophil)- and ED1 (macrophage)-positive cells. The postexercise increase in leukocyte infiltration was completely (p < 0.05) attenuated with estrogen supplementation alone in both muscle types, relative to sham. Progesterone treatment alone also resulted in a smaller (20%-30%) but significant (p < 0.05) attenuation of postexercise muscle leukocyte infiltration. The combination of estrogen and progesterone treatment did not significantly alter the attenuation seen with estrogen supplementation alone. Hence, progesterone can independently attenuate postexercise muscle leukocyte infiltration, albeit to a lesser degree than estrogen, and it will not negate or accentuate the effect of estrogen.

Estrogen influences satellite cell activation and proliferation following downhill running in rats.

To investigate the influence of estrogen on postexercise muscle repair processes, we examined the effects of estrogen supplementation (0.25-mg pellet) on numbers of myofibers positive for markers of total, activated, and proliferating satellite cells in rat skeletal muscles 72 h following downhill running. Ovariectomized female rats (n = 44) were divided into four groups (n = 11 per group): sham (no estrogen) controls (SC); sham, exercised (SE); estrogen-supplemented controls (EC); and estrogen-supplemented, exercised (EE). After 8 days of estrogen exposure, animals were exposed to 90 min of treadmill running at 17 m/min (-13.5 degrees ). Seventy-two hours later, soleus and white vastus muscles were removed and immunostained for total [paired box homeotic gene 7 (Pax7)], [activated myogenic differentiation factor D (MyoD)], and proliferating [5-bromo-2'-deoxyuridine (BrdU)] satellite cells. beta-Glucuronidase activity was increased (P < 0.05) in both muscles following exercise; however, the postexercise elevations in enzyme activity were attenuated in the EE group compared with the SE group in the soleus (P < 0.05). Immunohistochemical analysis revealed that exercised groups displayed increased numbers of myofibers containing total, activated, and proliferating satellite cells compared with control groups (P < 0.05). Furthermore, greater numbers of fibers positive for markers of total, activated, and proliferating satellite cells were observed postexercise in EE animals compared with SE animals for both muscles (P < 0.05). The results demonstrate that estrogen may potentially influence post-damage repair of skeletal muscle through activation of satellite cells.