A.) The physiology of skeletal muscle hypertrophy involves the interaction and interplay of complex mechanisms and pathways. These complex systems affect the regulation of contributing factors such satellite cell activation, proliferation, and differentiation, immune system response and reactions, and growth factor proteins. Unfortunately, space does not allow for a comprehensive review of skeletal muscle hypertrophy, therefore, it is recommended the reader refer to the following review articles in this section for a more thorough understanding of the topic. However, what is presented below is a brief overview of these regulating factors involved with skeletal muscle hypertrophy.
 
Satellite cells function to facilitate growth, maintenance and repair of damaged skeletal  muscle tissue  These cells are termed satellite cells because they are located on the outer surface of the muscle fiber, in between the sarcolemma and basal lamina (uppermost layer of the basement membrane) of the muscle fiber. Satellite cells have one nucleus, with constitutes most of the cell volume. Interestingly, satellite cells become activated when the muscle fiber receives any form of trauma, damage or injury, such as from resistance training overload. The satellite cells then proliferate or multiply, and the daughter cells are drawn to the damaged muscle site. They then fuse to the existing muscle fiber, donating their nuclei to the fiber, which helps to regenerate the muscle fiber. It is important to emphasize the point that this process is not creating more skeletal muscle fibers (in humans), but increasing the size and number of contractile proteins (actin and myosin) within the muscle fiber. This satellite cell activation and proliferation period lasts up to 48 hours after the trauma or shock from the resistance training session stimulus.

The immune system responds with a complex sequence of immune reactions leading to inflammation. The immune system causes a sequence of events in response to the injury of the skeletal muscle. Macrophages move to the injury site and secrete cytokines, growth factors and other substances. Cytokines are proteins which serve as the directors of the immune system. They are responsible for cell-to-cell communication. Cytokines stimulate the arrival of lymphocytes, neutrophils, monocytes, and other healer cells to the injury site to repair the injured tissue.

Growth factors are also involved with this process, which include hormones and cytokines, that are very involved in muscle hypertrophy. Growth factors stimulate the division and differentiation of a particular type of cell. In regard with skeletal muscle hypertrophy, growth factors of particular interest include insulin-like growth factor (IGF), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF). These growth factors work in conjunction with each other to cause skeletal muscle hypertrophy. IGF is a hormone that is secreted by skeletal muscle. It regulates insulin metabolism and stimulates protein synthesis.  In response to progressive overload resistance exercise, IGF-I levels are substantially elevated, resulting in skeletal muscle hypertrophy. In addition, Growth hormone (GH) is a peptide hormone that stimulates IGF in skeletal muscle, promoting satellite cell activation, proliferation and differentiation. Lastly, Testosterone, can stimulate growth hormone responses in the pituitary gland, as well as increase the presence of neurotransmitters at the fiber site. Although the exact mechanism is still unknown, testosterone may have some type of regulatory effect on satellite cells.


References
 
1: Adams GR. Satellite cell proliferation and skeletal muscle hypertrophy. Appl Physiol Nutr Metab. 2006 Dec;31(6):782-90. Review.
 
2: Barton ER.  The ABCs of IGF-I isoforms: impact on muscle hypertrophy and implications for repair. Appl Physiol Nutr Metab. 2006 Dec;31(6):791-7. Review.
 
3: Folland JP, Williams AG.  The adaptations to strength training : morphological and neurological contributions to increased strength. Sports Med. 2007;37(2):145-68. Review.
 
4: Philippou A, Maridaki M, Halapas A, Koutsilieris M.
 The role of the insulin-like growth factor 1 (IGF-1) in skeletal muscle physiology. In Vivo. 2007 Jan-Feb;21(1):45-54. Review.
 
5: Joulia-Ekaza D, Cabello G.  The myostatin gene: physiology and pharmacological relevance. Curr Opin Pharmacol. 2007 Jun;7(3):310-5.