Changes in the protein composition of muscles of the rat in hypertrophy and atrophy.

Following denervation of skeletal muscle a number of changes occur. The most obvious of these is the progressive decrease in size or atrophy ofthe muscle. This involves a decrease in dry as well as wet weight of the tissue. That increase in size of a muscle may occur following section of the motor nerve was demonstrated in this laboratory by Martin & Sola (1948) and by Sola & Martin (1953). Approximately 7 days after section of the left phrenic nerve, increases in wet weight of from 25 to -55% were observed in the hemidiaphragm of the rat. These increases in wet weight were accompanied by increases in total dry weight and the term hypertrophy was therefore applied to the phenomenon. The hypertrophy proved to be transient; the muscle had returned to normal weight by about 30 days andthis was followedby typical atrophy of denervation. An attempt to duplicate the results in another laboratorywas reportedinabriefpaperbyThomson, Morgan & Brodish (1951). These workers found no increase in dry weight, although an increase in wet weight was observed folowing denervation of the left hemidiaphragm. They suggested the increase in weight was the result of oedema. In view of the lack of confirmation of the entire result, a more complete analysis appeared desirable, and in any case so unusual a response to denervation warranted further investigation. To be considered a true hypertrophy an increase in protein content, involving the fractions normally present, should be demonstrated. An increase of protein in muscle induced to hypertrophy by the administration of hormones has been described. Bigland & Jehring (1952) obtained hypertrophy of the quadriceps muscle of the rat by injection of growth hormone, but found no increase in total tension development. This led to the suggestion that the new material laid down was not contractile material. In part because of this observation, Hume (1952) repeated the work and confirmed the increase in total protein but found no change in the relative amounts of sarcoplasmic, contractile and connective tissue proteins. Similar results were obtained with * Writtenduringthetenure ofaU.S. PublicHealth Service Fellowship from the National Institute of Neurological Diseases and Blindness. Present address: Department of Zoology, Montana State University, Missoula, Montana. muscles in which hypertrophy was induced by growth hormone plus testosterone. Because a relative decrease in myofibrillarATPase activitywas observed which was not accompanied by a relative decrease in contractile protein, Hume suggested that the new protein at this stage might be a precursor of myosin. It was the purpose of the present research to determine whether the protein components of the denervated diaphragm increase during hypertrophy and whether in hypertrophy or atrophy there are changes in relative amounts of connective tissue, contractile and sarcoplasmic proteins. For comparison, analyses were made of the protein fractions in the normal levator ani muscle and in this muscle after hypertrophy induced by the administration of testosterone (Eisenberg, Gordon & Elliott, 1949).