Transferrin as a muscle trophic factor

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Abstract
Muscle cells grow by proliferation and protein accumulation. During the initial stages of development the participation of nerves is not always required. Myoblasts and satellite cells proliferate, fusing to form myotubes which further differentiate to muscle fibers. Myotubes and muscle fibers grow by protein accumulation and fusion with other myogenic cells. Muscle fibers finally reach a quasi-steady state which is then maintained for a long period. The mechanism of maintenance is not well understood. However, it is clear that protein metabolism plays a paramount role. The role played by satellite cells in the maintenance of muscle fibers is not known. Growth and maintenance of muscle cells are under the influence of various tissues and substances. Among them are Tf and the motor nerve, the former being the main object of this review and essential for both DNA and protein synthesis. Two sources of Tf have been proposed, i.e., the motor nerve and the tissue fluid. The first proposal is that the nervous trophic influence on muscle cells is mediated by Tf which is released from the nerve terminals. In this model, the sole source of Tf which is donated to muscle cells should be the nerve, and Tf should not be provided for muscle fiber at sites other than the synaptic region; otherwise, denervation atrophy would not occur, since Tf provided from TfR located at another site would cancel the effect of denervation. The second proposal is that Tf is provided from tissue fluid. This implies that an adequate amount of Tf is transferred from serum to tissue fluid; in this case TfR may be distributed over the entire surface of the cells. The trophic effects of the motor neuron have been studied in vivo, but its effects of myoblast proliferation have not been determined. There are few experiments on its effects on myotubes. Most work has been made on muscle fibers, where innervation is absolutely required for their maintenance. Without it, muscle fibers atrophy, although they do not degenerate. In contrast, almost all the work on Tf has been performed in vitro. Its effects on myoblast proliferation and myotube growth and maintenance have been established; myotubes degenerate following Tf removal. But its effects on mature muscle fibers in vivo are not well understood. Muscle fibers possess TfR all over on their cell surface and contain a variety of Fe-binding proteins, such as myoglobin. It is entirely plausible that muscle fibers require an amount of Tf, and that this is provided by TfR scattered on the cell surface.(ABSTRACT TRUNCATED AT 400 WORDS)