Preface

There are few ebooks available contains details on the integration of cellular apoptosis and sex steroids at the molecular level. Here, our intention is to show how hormonal signals activate cellular responses that have been discovered individually but, in reality when a signal reaches a cell those signaling cascades interact with all cellular components to different degrees. Therefore, with this work, we want to present in an integrated way the concepts of hormonal regulation and apoptosis. Moreover, it is important to know how these processes are at the molecular level since mistakes in them lead to pathologies. The present work centers on the role of 17b-Estradiol (E2) and Testosterone (T) in most animal tissues, in addition to the reproductive system. Highlighting the role of both hormones in the lifespan of the skeletal muscle 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 ubiquitously expressed. Moreover, ER and AR may have non-classical intracellular localizations, e.g. plasma membrane, mitochondria, and endoplasmic reticulum, raising complexity to the actions of E2 and T. As well as genomic actions, sex steroids can fast regulate signaling pathways by non-genomic mechanisms through ER and AR, too.

We continue describing basic concepts of programmed cell death and how both sex hormones can regulate apoptosis through those signaling pathways. In mitochondria, the existence of ER and AR and actions of estrogen and androgen have been demonstrated, in keeping with the organelle being the main switch point of programmed cell death. The recurrent action for each steroid hormone is the safeguard of mitochondria against diverse insults, resulting in cellular survival. Then we explain the role of sex hormones in mitochondrial physiology (ROS production, regulation of mitochondrial enzymes and oxidative system pathway). In addition, 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 sex hormones, mitochondrial dysfunction, increased apoptosis, depletion in muscle stem cells, augmented production of cellular toxins as ROS, and anomalous regulation of stress pathways) 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 is unclear, evidence suggests that the putative molecular mechanism associated with this condition could be apoptosis. Remarkably, sarcopenia has been linked to a deficit of sex hormones, which decrease upon aging. The skeletal muscle capability to repair and regenerate itself would not be possible without satellite cells, a subpopulation of cells that remain quiescent throughout life. In response to stress, this muscle stem cells are activated directing skeletal muscle regeneration. Of relevance, satellite cells are E2 and T target. To end, the last chapter is devoted to natural compounds that have similarity with sex hormones and that could, therefore, have therapeutic potential. Finally, I thank the people who collaborated in this work and I hope that it fulfills the objective of presenting an integrated vision of the cellular mechanisms that are activated in response to hormones, regulating apoptosis specifically in the skeletal muscle.

Andrea Vasconsuelo
Instituto de Ciencias Biológicas y Biomédicas del Sur (INBIOSUR),
Universidad Nacional del Sur- CONICET,
Bahía Blanca,
Argentina