Here are 3 studies on how estrogen can prevent muscle wasting and improve mitochondrial function.
Skeletal muscle weakness occurs with aging and in females this is compounded by the loss of estrogen with ovarian failure.
Estrogen deficiency mediates decrements in muscle strength from both
- inadequate preservation of skeletal muscle mass and
- decrements in the quality of the remaining skeletal muscle.
Processes and components of skeletal muscle that are affected by estrogens are beginning to be identified.
This review focuses on mechanisms that contribute to the
- loss of muscle force generation when estrogen is low in females, and
- conversely the maintenance of strength by estrogen
Evidence is accumulating that estrogen deficiency induces apoptosis in skeletal muscle contributing to loss of mass and thus strength. Estrogen sensitive processes that affect quality, i.e., force generating capacity of muscle, include myosin phosphorylation and satellite cell function.
Though I didn’t have access to the full-text article above, this next full article explains it in the context of cancer treatment:
The Effect of Estradiol Administration on Muscle Mass Loss and Cachexia Progression in Female ApcMin/+ Mice – free full-text article /PMC6838005/ – Nov 2019
Cancer cachexia is a multifactorial muscle wasting condition characterized by severe body weight and muscle mass loss which is secondary to chronic disease.
The mechanistic examination of cachexia has predominately focused on the male phenotype and created significant gaps in understanding cachexia progression in the female.
Female hypogonadism can accompany cancer cachexia and is characterized by reduced circulating 17ß-estradiol and uterine atrophy.
Estrogen has known functions in skeletal muscle homeostasis involving the
- regulation of muscle protein turnover,
- cellular stressors, and
- oxidative metabolism.
However, 17ß-estradiol’s ability to regulate cachexia progression in the female is not known. The purpose of this study was to determine the effect of gonadal function and estradiol administration on muscle mass loss and cachexia progression in female ApcMin/+ mice.
We report that E2 administration prevented
- body weight loss,
- muscle mass loss,
- cage inactivity, and
- grip strength loss
associated with cachexia.
In skeletal muscle, E2 reduced skeletal muscle AMPK phosphorylation, improved mTORC1 signaling, and prevented mitochondrial dysfunction.
Our results demonstrate a role for 17ß-estradiol for the prevention of skeletal muscle mass loss in female tumor bearing mice. Furthermore, 17ß-estradiol prevented cachexia’s disruption in skeletal muscle signaling involving AMPK and mTORC1, in addition to improving mitochondrial function in female tumor bearing mice.
Interestingly, 17ß-estradiol administration increased relative food intake in MIN mice, which was likely involved in the prevention of muscle mass loss.
The beneficial effects of 17ß-estradiol administration in ovariectomized MIN mice suggest that ovarian function is not necessary for the beneficial effects on cachexia progression, and has significant therapeutic implications since most woman that develop cachexia are hypogonadal
Skeletal muscle mass is maintained by the balanced regulation of protein synthesis and degradation, and cancer-induced disruption to this regulation is a well-established driver of cachexia
estradiol improved protein synthesis further confounding the implications of estradiol in skeletal muscle signaling in a non-diseased state
Skeletal muscle mitochondrial dysfunction has been widely investigated as a critical driver of muscle wasting with cancer and aging.
Estrogen is an established modulator of muscle mitochondrial biogenesis and mitophagy, induces mitochondrial gene expression, and improves ATP turnover
- Reduced physical activity is a common altered behavior in pre-clinical models of cancer cachexia and cachectic patients
- and decreased activity level can impact mitochondrial function.
17ß-estradiol administered to MIN mice prevented physical activity loss which accompanies cachexia progression, and it has been reported that in OVX mice, estradiol improved voluntary wheel activity, thus having significant clinical implications.
Our findings support a role for 17ß-estradiol administration in the prevention of cachexia in the female MIN mouse.
Mitochondrial Metabolism: Pleiotropic actions of estrogen: a mitochondrial matter – free full-text article /PMC3568881/ – Feb 2013
Estrogen provides many beneficial effects early in life by regulating normal tissue development and several physiological functions. While
- estrogen replacement therapy (ERT) in women was expected to reduce the health risks associated with the age-related decline in estrogen levels during menopause,
- ERT also resulted in increased progression to other types of diseases.
Once again, everything seems to affect everything else and changes have complicated ripple effects we cannot predict.
Hence, distinguishing the signaling pathways that regulate the beneficial and detrimental effects of estrogen is important for developing interventions that selectively harness the hormone’s beneficial effects, while minimizing its side effects.
Estrogen can minimize mitochondrial dysfunction, which is thought to contribute to aging phenotypes.
Decline in estrogen levels during menopause may lead to progressive mitochondrial dysfunction and may permanently alter cellular response, including that of estrogen.
This looks like a classical “downward spiral”: less estrogen leads to less mitochondrial function, which leads to less response to estrogen, which leads to less mitochondrial function…
This review discusses the interplay between estrogen and mitochondrial function during the aging process and suggests a potential role of mitochondria in influencing the pleiotropic action of estrogen.
Early in life, estrogen provides several beneficial effects, including
- preserving mitochondrial integrity and
- maintaining normal physiological function
However, accumulation of mitochondrial dysfunction during aging leads to increased cellular senescence. In turn, accumulation of senescent cells can alter cellular signaling, such as estrogen response, resulting in increased risk to various diseases
The interplay between estrogen and mitochondrial function during the aging process may partly explain the pleiotropic action of estrogen.
Hence, further investigation in this area may provide insights into how to properly prescribe estrogen regimens in young or older individuals.