Mechanisms behind estrogen's beneficial effect on muscle strength in females - PubMed (original) (raw)

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Mechanisms behind estrogen's beneficial effect on muscle strength in females

Dawn A Lowe et al. Exerc Sport Sci Rev. 2010 Apr.

Abstract

Muscle weakness ensues when serum testosterone declines with age in men. Testosterone's female counterpart, estrogen, also has been implicated in age-related strength loss, but these results are less conclusive. Our working hypothesis is that estrogens do benefit muscle strength, and that the underlying mechanism involves estrogen receptors to improve muscle quality more so than quantity.

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Figures

Figure 1

Figure 1

Relationship between specific muscle force of the adductor pollicis muscle and age for groups of subjects that did and did not experience loss of estrogens during the sixth decade of life. Within each graph, specific force is expressed as a percent of the mean for subjects aged 45 yr and younger. Top panel: Following menopause, women lose muscle strength with age at a greater rate than do men out until about the age of 70 yr. Bottom panel: Postmenopausal women who take an estrogen-based hormone therapy (HT) retain muscle strength to a greater extent than do women who do not take the therapy. Figure created from data originally published in (22).

Figure 2

Figure 2

Forest plots of effect sizes from meta-analyses on studies that reported muscle strength normalized to muscle size (specific force) in subjects that were and were not estrogen deficient. Each square represents the effect size for that study with the size of the square equating to the weight of that study in the meta-analysis. The horizontal line through the square indicates the 95% confidence interval (CI) for that effect size. Within each plot, studies are arranged from lowest to highest effect sizes. Top panel: Results of five studies on postmenopausal women comparing muscle strength between women who were and were not on an estrogen-based hormone therapy. Bottom panel: Results of seven studies on rats or mice comparing specific force between those that were estradiol deficient via ovariectomy and those that were ovary intact or estradiol-replaced. Figure created from data originally published in (8); refer to this paper for references cited in the figure.

Figure 3

Figure 3

Decrements in the functions of myosin occur when muscle fibers or myofibrils are analyzed from rodents deficient in estrogens via ovariectomy (OVX). Conversely, when ovariectomized rodents are treated with estradiol (OVX+E2), myosin functions return to control levels. Tension is specific force generated by permeabilized fibers and is reflective of the overall ability of acto-myosin filaments to make force (data from (32)). The fraction of myosin in the strong-binding structural state during contraction directly reflects the force-generating capacity of myosin and active stiffness of intact muscle indirectly reflects myosin strongly bound to actin during contraction; both are affected by estrogen status (data from reference #16). Both myofibrillar adenosine triphosphate hydrolysis (ATPase) and control of calcium (Ca2+) are required for myosin to cycle between strong- and weak-binding states to actin and both are influenced by estrogens (data from (33)).

Figure 4

Figure 4

Schematic of how estrogens may benefit muscle strength. Ovariectomized mice display a reduction in muscle strength and this is attributed to a decrement in the fraction of strong-binding myosin during contraction. Conversely, treatment with estrogens increases strong-binding myosin and ultimately strength. Estrogen receptor (ER) content in muscle is responsive to circulating estrogens, and we hypothesize that ERs may initiate signaling cascades and/or regulate genes that result in an overall reduction in oxidative stress in fibers. Alternatively, estrogens may have some direct antioxidant affect. We speculate that reducing oxidative stress would preserve myosin structure-function, conferring a beneficial effect on strength. Solid arrows represent experimental evidence from our lab and others. Dashed arrows represent hypothesized mechanisms of estrogens’ actions in skeletal muscle. Abbreviations: adenosine triphosphate (ATP), inorganic phosphate (Pi), G protein-coupled receptor (Gper).

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