The fine structure of rat gastrocnemius muscle fibers has been studied after changes were induced in the basal metabolic rate (BMR) by thyroidectomy and L-thyroxine administration under anabolic conditions. Biochemical analysis of skeletal muscle mitochondrial respiration and phosphorylation from the same tissue preparations has been summarized, details having been published earlier (3). As estimated from electron micrographs, the total amount of mitochondria from thyroidectomized animals was enlarged 1.5 times over that from normal controls. The total amount of mitochondria from thyroidectomized or normal animals made hypermetabolic with thyroxine was increased 2.5 to 3.5 times over that from their corresponding controls. In all cases, there was an increase in the mitochondrial population and the profile ratio of cristae to matrix was also considerably increased, thus indicating both relative and absolute enlargements of the entire surface of the cristae per unit fiber. The major structural changes persisted for at least 3 weeks after the cessation of thyroxine treatment, by which time the elevated mitochondrial respiratory and phosphorylative activity had declined to normal values. The hypertrophy and increase in mitochondrial population was more prominent in the perinuclear and subsacrolemmic regions near blood vessels than in the interstices of the fibrils. The very long interfibrillar mitochondria found in both the hypo- and hypermetabolic tissues are more likely to be derived from outgrowths of the original mitochondria rather than from a fusion of smaller ones. These findings are compatible with the ideas expressed elsewhere (see 1, 3, 10) that, under conditions close to the physiological, thyroid hormones control mitochondrial metabolic activity by a subtle alteration in mitochondrial composition with respect to their respiratory and phosphorylative constituents. The possible application of using thyroid hormones in the study of biogenesis of mitochondria and the synthesis of mitochondrial constituents are discussed.

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