The Cellular Basis for Skeletal Muscle Growth Retardation (Undernutrition)

136 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1985.Attempts to explain the basis for permanent growth retardations often focus on the cell number/cell size hypothesis. According to this hypothesis, undernutrition produces irreversible effects if and only if it occurs during the time of rapid DNA accretion. If tissue DNA contents are used to estimate cell number, then growth retardation is characterized by fewer cells. Because total tissue DNA content appears to be a good estimate of cell number only in tissues with mononucleated cells, use of this technique for tissues (e.g. skeletal muscles) with multinucleated cells may not be appropriate. The primary purpose of the present research was to re-evaluate the cell number/cell size hypothesis and its application to skeletal muscle. Biochemical and morphological determinations were performed on the same muscle to compare the results from these two measurements of muscle cellularity. Growth retardation of male rats was examined in three experiments. Undernutrition slowed muscle growth and retarded accretion of protein and DNA, but did not change muscle fiber number. Essentially no change was seen in the ratio of protein/DNA while fiber diameter and length were small. In the third experiment male rats were food-restricted from birth until 120 days and then refed until 316 days. Muscle weights were about 50% smaller than average at 120 days and remained about 16% smaller after long-term refeeding. Partial recovery of muscle protein and DNA occurred because the period for accretion of protein and DNA was extended beyond the usual time frame. Skeletal muscles of the growth-retarded rats were characterized by smaller, not fewer, fibers which contained smaller numbers of nuclei. Deficits in longitudinal and radial muscle growth accounted for approximately 25 and 75%, respectively, of the growth stunting. Neither muscle cell number nor size should be estimated from the biochemical measurements of total muscle DNA and the ratio of protein/DNA.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD