Sex Steroids and Apoptosis In Skeletal Muscle: Molecular Mechanisms

MILANESI L.,; FARAONI M.B.,; VASCONSUELO A.,; MUSSO F.,; PRONSATO L.,

Bentham

Año: 2019 p. 168

978-9-81141-235-6

There are few ebooks available contains details on the integration of cellular apoptosis andsex steroids at the molecular level. Here, our intention is to show how hormonal signalsactivate cellular responses that have been discovered individually but, in reality when a signalreaches a cell those signaling cascades interact with all cellular components to differentdegrees. Therefore, with this work, we want to present in an integrated way the concepts ofhormonal regulation and apoptosis. Moreover, it is important to know how these processes areat the molecular level since mistakes in them lead to pathologies. The present work centers onthe role of 17b-Estradiol (E2) and Testosterone (T) in most animal tissues, in addition to thereproductive system. Highlighting the role of both hormones in the lifespan of the skeletalmuscle cell.First, we describe the role of E2 and T affecting growth and cell functions in mammals.Accordingly, the nuclear estrogen (ER) and androgen (AR) receptors are ubiquitouslyexpressed. Moreover, ER and AR may have non-classical intracellular localizations, e.g.the plasma membrane, mitochondria, and endoplasmic reticulum, raising complexity to theactions of E2 and T. As well as genomic actions, sex steroids can fast regulate signalingpathways by non-genomic mechanisms through ER and AR, too.We continue describing basic concepts of programmed cell death and how both sex hormonescan regulate apoptosis through those signaling pathways. In mitochondria, the existence ofER and AR and actions of estrogen and androgen have been demonstrated, in keeping withthe organelle being the main switch point of programmed cell death. The recurrent action foreach steroid hormone is the safeguard of mitochondria against diverse insults, resulting incellular survival. Then we explain the role of sex hormones in mitochondrial physiology(ROS production, regulation of mitochondrial enzymes and oxidative system pathway). Inaddition, we describe the action of sex hormones on muscle stem cells at the molecular level.The book shows how the integration of all the processes described (the effects of sexhormones, mitochondrial dysfunction, increased apoptosis, depletion in muscle stem cells,augmented production of cellular toxins as ROS, and anomalous regulation of stresspathways) results in sarcopenia. Sarcopenia is a predominant disorder among the elderly,which implies the loss of muscle mass and strength. Although the basis of sarcopenia isunclear, evidence suggests that the putative molecular mechanism associated with thiscondition could be apoptosis. Remarkably, sarcopenia has been linked to a deficit of sexhormones, which decrease upon aging. The skeletal muscle capability to repair and regenerateitself would not be possible without satellite cells, a subpopulation of cells that remainquiescent throughout life. In response to stress, these muscle stem cells are activated directingskeletal muscle regeneration. Of relevance, satellite cells are E2 and T target. To end, the lastchapter is devoted to natural compounds that have similarity with sex hormones and thatcould, therefore, have therapeutic potential. Finally, I thank the people who collaborated inthis work and I hope that it fulfills the objective of presenting an integrated vision of thecellular mechanisms that are activated in response to hormones, regulating apoptosisspecifically in the skeletal muscle.