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Group VI - Skeletal Muscle

Group VI - Skeletal Muscle

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Published by iqbal tambunan
Dari Prof. Dr. Herbert SIpahutar M.Sc.,M.Si
sebagai tugas fisiologi hewan.
Dari Prof. Dr. Herbert SIpahutar M.Sc.,M.Si
sebagai tugas fisiologi hewan.

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Categories:Types, Research, Science
Published by: iqbal tambunan on Apr 04, 2012
Copyright:Attribution Non-commercial


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32:120-126, 2008. doi:10.1152/advan.90111.2008
 Advan Physiol Educ
Marybeth Brown
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30 articles, 11 of which you can access free at:This article citeshttp://ajpadvan.physiology.org/cgi/content/full/32/2/120#BIBL3 other HighWire hosted articles:This article has been cited by[PDF] [Full Text] [Abstract] , January 1,2009; 18(1): 331-336.
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on the following topics:http://highwire.stanford.edu/lists/artbytopic.dtlcan be found at Medline items on this article's topics Physiology .. Aging and Reproductive EndocrinologyPhysiology .. BonePhysiology .. TestosteronePhysiology .. EstrogenDevelopmental Biology .. AgingBiochemistry .. Steroidsincluding high-resolution figures, can be found at:Updated information and serviceshttp://ajpadvan.physiology.org/cgi/content/full/32/2/120can be found at:
 Advances in Physiology Education
aboutAdditional material and informationhttp://www.the-aps.org/publications/advanThis information is current as of January 28, 2010 .
http://www.the-aps.org/.American Physiological Society. ISSN: 1043-4046, ESSN: 1522-1229. Visit our website atDecember by the American Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright © 2005 by thecourses and in the broader context of general biology education. It is published four times a year in March, June, September andis dedicated to the improvement of teaching and learning physiology, both in specialized
 Advances in Physiology Education
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Staying Current
Skeletal muscle and bone: effect of sex steroids and aging
Marybeth Brown
Center for Gender Physiology, Physical Therapy Program, Biomedical Sciences, University of Missouri, Columbia, Missouri
Submitted 14 February 2008; accepted in final form 14 February 2008
32:120–126,2008;doi:10.1152/advan.90111.2008.—Bothestrogen and testosterone are present in males and females. Bothhormones contribute to the well being of skeletal muscle and bone inmen and women, and there is evidence that the loss of sex hormonesis associated with the age-related decline in bone and skeletal musclemass. Hormonal supplementation of older adults to restore estrogenand testosterone levels to those of young men and women is notwithout penalty.estrogen; testosterone
, the relevance and importance of female and male sex hormones for the health and well being of skeletal muscle and bone have become recognized. Althoughthere are multiple sex hormones, those that have been studiedthe most are estrogen and testosterone. Both strogen andtestosterone are present in men and women, and both hormonesexert direct and indirect effects on skeletal muscle and bone inmen and women. As would be expected, testosterone valuesare high in men and low in women, and estrogen values arehigh in women and low in men.Aging results in a highly significant loss of estrogen inwomen and testosterone in men. Aging also reduces the levelof testosterone in women and estrogen in men. The pattern of decline differs by sex, with women showing a precipitous lossof estrogen during menopause and men losing testosteronecontinuously throughout life, starting in the third decade.Indeed, many men are hypogonadal by the eighth decade withfree testosterone levels below 320 pg/dl, the accepted mini-mum (11). Women become postmenopausal typically by thesixth decade, thus spending approximately one-third of theirlifetime in an estrogen-deficient state (8).In young men and women, there are a number of condi-tions that cause sex hormone levels to drop to nearlyundetectable levels, such as trauma, spinal injury, braininjury, and bed rest (e.g., Ref. 23). There is emergingevidence that a sedentary lifestyle and associated obesity arealso associated with low sex hormone levels in men, whichmay indicate that hypogonadism is on the rise in our society.The long-term consequences of low hormone levels at ayoung age have yet to be clearly defined.Because sex hormones are markedly reduced with age, andwe are living longer, there has been recent interest in restoringhormone levels to “normal” levels in aging men and women.As expected, bringing testosterone levels above 320 pg/dl inhypogondal old men has an anabolic effect on skeletal muscle.Significant gains in muscle mass and strength have beenrealized; however, testosterone hormone replacement in oldermen is not without penalty. Likewise, providing estrogen toolder women has an anabolic effect on bone, and possiblymuscle, but there may be negative consequences of givingestrogen to women in their 60s and 70s. A summary of theeffects of estrogen and testosterone is shown in Table 1.
 Direct Estrogen Effects on Skeletal Muscle in Women
There appear to be direct effects of estrogen on skeletalmuscle. Skeletal muscle has estrogen receptors (ERs) on thecell membrane, in the cytoplasm, and on the nuclear mem-brane. It is believed that estrogen exerts direct effects onskeletal muscle through ER
, but there is a possibility thatestrogen influences the maintenance and well being of skeletalmuscle using other pathways such as the IGF-1 receptor-mediated pathway. Recently, a second ER type was discoveredin skeletal muscle (ER
), but its function is largely unknown,particularly in humans.In young women and young rats, estrogen has an effect onmuscle metabolism. Indeed, women have more endurance thanmen in long-distance running events, using less glycogen andmore fat as fuel than men. Male rats given estrogen can runlonger distances on a treadmill. Estrogen has also been shownto protect younger women from muscle injury apparently bystabilizing the muscle membrane (28). Whether the glycogen-sparing effects of estrogen (muscle endurance) and the protec-tion of muscle from injury are lost with menopause is largelyunexplored. It does appear anecdotally that postmenopausalwomen are more susceptible to muscle injury.Is there an accelerated loss of skeletal muscle with meno-pause? Cross-sectional studies have suggested that women mayhave a faster rate of loss in muscle mass and strength during theperimenopausal years (Fig. 1). Additionally, skeletal musclehas a higher proportion of ER
on type II or fast twitch musclefibers, which may be one reason for the greater loss in type IImuscle fiber size with age. Type I or slow fibers maintain theirsize for most of a woman’s lifetime, whereas type II fibersbegin to show atrophy in the fifth decade. It is tempting tospeculate that the loss of estrogen is associated with the declinein muscle mass with aging, but the literature is difficult tointerpret. There are a number of studies that support an asso-ciation of muscle mass and estrogen and others that find noassociation between estrogen and muscle mass and strength.An example of a study in which there was no association of estrogen and muscle mass was reported by Hansen et al. (13).Women in this study were given 20-mg doses of estrogen for64 wk, and the increase in muscle mass was not significant(
0.09). It should be noted, however, that fat mass de-creased and bone mass increased significantly in subjects thatreceived estrogen. Conversely, Sørenson et al. (26) performeda 12-wk double-blind crossover study where estrogen or pla-cebo was administered, there was a 16-wk washout period, andwomen were then given whichever drug (estrogen or placebo)they had not received during the first 12 wk. There was asignificant increase in lean mass during the estrogen phase.
Address for reprint requests and other correspondence: M. Brown, PhysicalTherapy Program, School of Health Professions, 106 Lewis Hall, Columbia,MO 65211 (e-mail: brownmb@health.missouri.edu).
 Adv Physiol Educ
32: 120–126, 2008;doi:10.1152/advan.90111.2008.120 1043-4046/08 $8.00 Copyright © 2008 The American Physiological Society
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Overall, the strength of evidence in support of an anaboliceffect of estrogen on skeletal muscle via meta-analysis out-weighs the evidence of no effect (2, 20).One question that has surfaced recently is whether theaccelerated loss in muscle mass with menopause is due to adecline in testosterone (total and free) rather than a decline inestrogen. Testosterone does decrease with age, but serumvalues of testosterone show the greatest decline before meno-pause and little additional change during menopause (8). Thus,there does not appear to be a relationship between muscle massloss and lower levels of testosterone with menopause.Most of the clinical trials that support an anabolic estrogeneffect on skeletal muscle in women have tended to haveyounger subjects. There may be less of an effect of estrogenwith advancing age, but the strength of evidence to support thiscontention is minimal. Two studies (5, 15) bring into questionthe effect of estrogen in older women. In one study, theincidence of sarcopenia (age-related muscle mass loss) wasinvestigated in older women who had been on hormone re-placement therapy (HRT) for at least 2 yr. Women on HRT hada 23% incidence of sarcopenia, whereas those not on HRT hada 22% incidence. As is the case with most studies of olderwomen, the dose of estrogen differed among subjects, andthere were a number of variables not accounted for, such asactivity levels, diet, and medications. Sarcopenia takes years todevelop, and it is possible that the potential benefit of HRT hadnot begun to show in just 2 yr of intervention. In anotherexercise study, older women were aerobically trained for 9 mo.Half of the subjects began HRT at the beginning of training. Atthe end of 9 mo, strength gains for women on HRT were thesame as the gains made by women who were not on HRT (16%vs. 17%). Women in this study performed weight-bearing exer-cise, however, not resistance exercise, and it could be argued thatthe exercise stimulus was not sufficiently intense to augment theestrogen effect. In summary, possible estrogen effects on skeletalmuscle in older women are not well understood.To amplify the potential anabolic effect of estrogen onskeletal muscle, we chose a rat model in which we couldcombine loss of ovarian hormones with inactivity. The reason-ing behind this approach is that if ovarian hormones, notablyestrogen, influence muscle mass and function, then the com-bination of ovariectomy (Ovx) and inactivity should result ingreater muscle atrophy than either condition alone. We alsohypothesized that recovery from a bout of inactivity would bedelayed in those rats without ovarian hormones. To induceinactivity, we used a technique called hindlimb unweighting,which simulates bed rest (Fig. 2). The hindlimbs are free tomove, as in bed rest, but not bear weight. Rats were kept in thissimulated bed rest condition for 28 days. Some rats werestudied as controls and some were studied following theunweighting, and the remaining rats were studied following 2wk of recovery from 4 wk of unweighting. Results for arepresentative hindlimb muscle, the gastrocnemius, are shownin Fig. 2. Briefly, rats with intact ovaries and those that wereOvx experienced the same degree of muscle atrophy withunweighting. In Ovx rats, however, atrophy persisted duringrecovery, with no evidence of an increase in muscle mass (6).To verify this finding, we unweighted another group of Ovxrats for 4 wk and allowed half of the rats to recover for 2 wk.In both Ovx groups, we restored estrogen values to withinnormal limits using estrogen implants. Gastrocnemius re-growth in the Ovx-estrogen-supplemented rats showed thesame magnitude of muscle mass regrowth as intact rats, sug-gesting that estrogen was necessary to stimulate muscle re-growth following atrophy (Fig. 2
). To further pursue thispossibility, we examined the Akt/mammalian target of rapamycinpathway, which is critical for muscle protein synthesis. In theOvx-recovery rats, there was a failure to turn on the Akt pathway(Fig. 2C, no phosphorylation of Ser
), suggesting that estrogenis necessary to regrow muscle that has undergone atrophy. Theseresults suggest that estrogen stimulates muscle regrowth, possiblythrough the ER or possibly through estrogen stimulation of theIGF-1 receptor (25). If these findings of failure to reverse muscleatrophy are representative of what happens in women who un-dergo periods of bed rest due to illness, there is cause for concern.Women lose
50% of available muscle mass with normal aging,which is barely enough muscle mass and strength to functionthroughout the normal lifespan. Life events that potentially in-crease age-related muscle loss put women at even greater risk forloss of independence. Whether rehabilitation exercise can stimu-late complete regrowth of atrophic muscle in the absence of estrogen is unknown.Recently, a more basic approach to studying estrogen-de-prived muscle was taken using Ovx mice. Using electronparamagnetic spin microscopy, a new technique, Moran andcolleagues (18) determined that the muscle mass and quantityof contractile protein were unchanged in Ovx animals butmuscles from Ovx mice generated less contractile tensionbecause the interaction between actin and myosin, the essentialcontractile elements, was altered.In summary, there is considerable confusion in the literaturerelated to direct estrogen effects on muscle mass and strength,but it can be reasonably concluded that estrogen does influencemuscle mass in younger women and loss of estrogen negativelyimpacts contractile function. A summary of the direct effects of estrogen on skeletal muscle in women is shown in Table 2.
Fig. 1. Current world records for bench press for drug-tested women in the148-lb weight class. Note the accelerated rate of strength loss that occursduring the menopause years even in women who are highly trained. [From theAmerican Power Lifting Association.]
Table 1.
Summary of the effects of estrogen and testosterone
Testosterone and estrogen:
Are both present in males and females
Influence the quantity of bone and muscle in men and women
Decrease with age in both sexes
Decrease significantly with common clinical conditions, such as trauma,obesity, and hysterectomy.
Staying Current
 Advances in Physiology Education
VOL 32
JUNE 2008
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