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Muscle, the major conçonent o f lean body tissue and the largest protein store in the body, is capable of undergoing rapid and extensive alterations in mass. Such alteration in the growth o f this tissue can be produced in response to a variety of different stimuli, including altered nutritional and endocrine status as well as neural and mechanical influences.

Growth of muscle can occur in two ways: (1) by an increase in muscle cell number, (2) by an increase in muscle cell size. Both of two mechanisms are involved in muscle growth. Growth in cell number, however, is limited to the prenatal and immediately period, with the animals and human being bom with or soon reaching their full conq)lement o f muscle cells. Postnatal muscle growth is frequently considered to be due primarily to muscle cell hypertrophy, as contrasted to prenatal muscle fibre hyperplasia (Allen et al, 1979)

1.8.1. Muscle Developmental growth

With one or two exceptions, skeletal muscle is derived from lateral plate and paraxial somitic mesoderm. The main mass of muscle arises from the inner part o f each myotome. As soon as the myoblast occurs it will differentiate into myotube, the latter develops to the small phase fibre and fibre number becomes fixed before birth or

shortly after birth. During the post-natal growth o f the animal, the growth of muscle occurs only due to muscle fibre increase in size. Muscle fibre hypertrophy happens in two ways: (1) by increase in length and (2) by increase in circumference or girth.

A. Growth in the length of myofibrils: The limbs of most species of animals increase in length by several times during post-natal growth. The increase in limb length is accompanied by an increase in the fibres o f individual muscles o f the limb. It has been shown that increase in muscle fibre length is a consequence o f an increase hi the number o f sarcomeres. Williams and Goldspink (1971) have shown that longitudinal growth in vertebrate muscle takes place by adding to the number of

sarcomeres in series. Griffin et al (1971) demonstrated that the end o f the muscle fibres are growth regions. Using such data, Goldspink (1983) demonstrated that the number o f sarcomeres in the postnatal soleus muscle o f the mouse increases from about 700 to 2200 in 0 to 20 weeks o f age. Most o f the increase actually occurred during the first 7 weeks of age, which coincides with the rapid growth phase of the mouse. Goldspink (1983) has also indicated that extra long sarcomeres are added to the ends of the myofibrils. Adaptation in sarcomere numbers for the growing animals is of significance physiologically since the degree o f force that a muscle can generate is dependent on the degree o f overlap by the thick and thin filaments. Thus, the optimum sarcomere length is that which allows the maximum amount of interaction between the myosin cross bridges and the actin filaments. Since the length o f both the thick and thin filaments are fixed, the only mechanism by which the muscle fibre can adjust its sarcomere length is to regulate the number of end-to-end sarcomeres in the myofibrils. It seems probable then that each muscle can sense when its mechanical output decreases and add or remove sarcomeres to maintain the maximum frmctional overlap o f the thick and thin filaments (Goldspiok, 1983). Thus, the amount of tension generated appears to be responsible for controlling the number o f in-series sarcomeres. But the signals including any putative growth frctor which links the force or tension generated and addition o f sarcomeres to the myofibrils remains to be elucidated.

B. G row th in fibre diam eter: The physiological reason for the conversion of the small phase fibres into large phase fibres becomes apparent when the ultrastructure of fibres in these two phases of development is examined. Indeed the increase in girth o f the fibre can be explained almost entirely by the increase in the number and size of the myofibrils, the number o f the myofibrils within an individual muscle fibre of the mouse may increase during growth by more than 15 times (Goldspink, 1970). Evidence obtained by examining muscle fibres at different stages o f growth strongly suggests that this proliferation of myofibrils is the result o f longitudinal sphtting of the existing myofibrils once they attain a certain size. It has been shown that muscle fibres increase in girth is in a discontinuous way (Alnaqeeb & Goldspink, 1987). In large muscles the fibres probably undergo several increase in size over a relatively long period o f time before they attain their ultimate size. The signal transduction involved in this process is not known yet.

1.8.2. Muscle compensatory growth

Like most organs of the body, muscle changes in mass with changes in physiological demand; increased work leads to rapid hypertrophy, while decreased work causes atrophy. These adaptive responses are probably o f important selective advantage to the organism and enable it to acquire new skill and to compensate for disease or injury (for example, cardiac hypertrophy). This hypertrophy is called compensatory growth.

In order to investigate the muscle compensatory growth, a simple and highly reproducible experimental system for inducing hypertrophy o f skeletal muscle was required. Goldberg (1967) used a method in which the gastrocnemius portion of the achilles tendon was sectioned on one limb of rat, leaving the remaining plantaris and soleus muscle to support the body weight on that side and which undergoes rapid in conq)ensatory growth. Using this method, twenty-four hours after operation increase in mass was aheady apparent and by the end of five days, it was essentially complete (as this is now beheved to be induced by stretch). Another simple procedure inducing

rapid muscle hypertrophy was designed by Goldspink et al (1992) in which the tibiahs anterior (TA) muscle o f rabbit was stretched by immobilization of one limb in the extended position. As the result the TA muscle is induced to synthesize much new protein and to grow by as much as 30% within a period as short as 4 days. This very rapid hypertrophy was found to be associated with an increase o f up to 250% in the RNA content o f the muscle.

A number of studies were undertaken to clarify the relationship between muscle postnatal growth and muscle compensatory growth. It has long been known that postnatal growth requires the presence of pituitary growth hormone (GH). But the pituitary growth hormone is not essential for muscle compensatory growth, as the same results o f muscle conq>ensatory growth were obtained in the hyp ophysectomized rats (Goldberg, 1967). Also muscle compensatory growth process can occur in animals deprived o f food and thus in negative nitrogen balance in a manner similar to that seen with normal animals (Goldberg & Goodman, 1969a). Together these findings suggest that compensatory hypertrophy clearly takes precedence over hormonal growth. The differences o f requirements for different muscle growth are summarized in Table 1.4.

Table 1.4

Muscle Developmental Growth Muscle Corqpensatory Growth Pituitary hormones (growth hormone,

TSH etc.)

Occurs in hyp ophysectomized (non­ growing) animals

Adequate diet Occurs in food-deprived animals

(despite general muscle wasting)

Although both of these different processes affect the composition o f the tissue in distinct ways (Goldberg & Goodman, 1969b), both involve increased protein and DNA synthesis in muscle.

Li order to look at fibre changes in the muscle which undergoing rapid hypertrophy by increased work load, Rowe and Goldspink (1968) using essentially the same procedure found that the mouse soleus muscle which normally has a unimodal distribution o f fibre sizes become bimodal. In this case the increased work load had not caused all the fibre to increase in size but caused a certain percentage of them to increase in cross-sectional area by 3 or 4 times. The response o f the muscle to different work load poses the question as to Wiat is the nature o f the link or feedback mechanism between the mechanical event and the biochemical processes involved in the synthesis o f more muscle proteins.