Physical exercise is a fundamental component for a healthy, balanced lifestyle as it provides a myriad of benefits to ones physiology and psychology. Exercise increases oxygen uptake, cardiovascular functional capacity, metabolism, respiratory function (Fletcher et al., 1996), and cognitive abilities (Lett et al., 2005). Such physical and neurological changes decrease one's risk of coronary heart disease, blood abnormalities, diabetes, obesity (Fletcher et al., 1996), and depression (Lett et al., 2005). Besides these benefits, many people also exercise to gain muscle mass so they can maximize their performance in a particular sport, or to better their body image and increase confidence and self esteem. The process of synthesizing muscle tissue is known as myogenesis, as muscle cells fuse together to form new muscle fibers (Okazaki & Holtzer, 1966).
Muscle cells are multinucleated (they contain multiple nuclei) as a result of this fusion, and contain specialized proteins that move when ATP is hydrolyzed (Freeman, 2005). Muscle cells can form three different types of muscle tissue: skeletal muscle, which contracts to move the skeleton; cardiac muscle, which makes up the walls of the heart; and smooth muscle, which lines the inside of organs and blood vessels (Freeman, 2005). Exercise builds new skeletal muscle fibers by employing multiple cellular mechanisms, such as action potentials that release neurotransmitters (Freeman, 2005). But it all starts with the mitogen activated protein kinase (MAPK) signaling system and a cascade of protein phosphorylation (Aronson et al., 1997).
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There are numerous growth factors and hormones that can stimulate receptor protein-tyrosine kinases (RTK's) and thus initiate this pathway (Aronson et al., 1997). Human growth hormone (HGH) is one example, and it has long been known that physical exercise increases the body's production of this hormone (Kraemer, 1990). As Stacy et. al. explain, "[HGH is] a protein secreted by cells called somatotropes in the anterior pituitary gland" (Stacy et al., 2004). When released it will bind to RTK's on muscle cell plasma membranes, causing them to come together and dimerize. Trans-auto phosphorylation then occurs, where the kinases on one receptor phosphorylate multiple tyrosine residues on the other. The adapter protein Grb can then bind to the phosphorylated tyrosine residues and in turn bind SOS, a nucleotide exchange factor. SOS, now on the plasma membrane and close to Ras (a lipid-anchored G-protein involved in cell proliferation), will catalyze it's exchange of GDP to GTP. Activated Ras then recruits Raf (a kinase) from the cytoplasm to the plasma membrane. Raf will phosphorylate the mitogen activated protein kinase kinase MEK., which will in turn phosphorylate extracellular regulated kinases (ERK's) (Karp, 2010).
Since ERK's contain a nuclear localization signal, they can enter the nucleus and activate multiple transcription factors for genes involved in cell proliferation and myogenesis (Aronson et al., 1997). Examples of such genes are cyclin-D1 (involved in cell growth) and MKP-1 (codes for MAPK phosphotases which shut down the pathway) (Karp, 2010). The transcription factor cAMP-responsive element binding protein (CREB) can also be phosphorylated in the nucleus, leading to various downstream effects needed for myogenesis (Aronson et al., 1997), such as gluconeogenesis (Karp, 2010). The major downstream consequence, however, is the expression of "unique molecular markers" on the surface of the muscle cell (Okazaki & Holtzer, 1966). This signals other muscle cells to cluster and fuse together, and is mediated by phagocytosis or a rearrangement of the plasma membrane (Okazaki & Holtzer, 1966). This is in essence how muscle tissue expands, but this process also initiates the synthesis of myosin, allowing for greater contraction of muscle fibres (Okazaki & Holtzer, 1966).
Unfortunately building muscle mass this way is relatively slow, and requires great amounts of nutrients and calories in addition to physical stress. It is possible, however, to speed up these processes through the use of artificial supplements. Recombinant HGH is often used by athletes and bodybuilders as a ergogenic aid, and has become one of the most abused drugs in sports (Jenkins, 2001). Recall that HGH is produced naturally by the body during development and exercise, and it is frequently used in medicine to treat patients with Turner's Syndrome (short stature) (Stacy et al., 2004). But it is now being used by both amateur and professional athletes, as well as by those who exercise recreationally. High doses are often injected without any sort of medical supervision, and often in conjunction with other substances such as anabolic steroids (Jenkins, 2001). Injecting one's self with HGH will result in a substantial increase in lean muscle mass through the normal cellular mechanisms (Jenkins, 2001).
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This comes at a heavy price, however. Numerous studies have shown that prolonged use of HGH can lead to respiratory disease, diabetes, abnormal metabolism, breast and colorectal cancer, and death (Jenkins, 2001). These diseases are often a result of a condition called acromegaly, characterized by enormous body size and enlargement of facial bones (Stacy et al., 2004). Excessive levels of HGH in the bloodstream will overstimulate receptors involved in the MAPK signaling system (which has a profound role in regulating cell proliferation) and thus lead to these severe and irreversible side effects. Broad social factors, such as persistent portrayal of "ideal" body types in advertising and films, are responsible for individuals attempting to enhance their physique through such dangerous methods. These individuals may also be suffering from a psychological disorder known as muscle dysmorphia, where they believe their muscles are considerably underdeveloped, when in reality the reverse is true. Many people in our society share a distorted body image, and so feel the need to take ergogenic aids such as HGH. These significantly override the beneficial effects of exercise, but hopefully new studies will emerge that shed some more light on their adverse side effects. This is why a basic understanding of the cellular mechanisms underlying hormones and intercellular signaling is required, and crucial. One would hope that these studies reach the public eye, so that everyone will begin (or continue) to exercise naturally and enjoy the many benefits it provides.