Lysosomal alterations in heart, skeletal muscle, and liver of hyperthyroid rabbits

Daily administration of L- or D-thyroxine for 1 week produced hypertrophy of the heart and atrophy of skeletal muscle and liver. The myocardial hypertrophy was accompanied by a rise in the activity of cathepsin D but not of cathepsin B; this was correlated with an increase in cathepsin-D-rich interstitial cells while the number of cathepsin-D-positive lysosomes in myocytes was decreased, as assessed from immunohistochemistry. In atrophying skeletal muscle (soleus and tibialis anterialis), large increases in the activities of cathepsins B and D were present. Immunohistochemical localization of cathepsin D revealed that in thyrotoxic striated muscle cells this acid proteinase had become localized diffusely in the paranuclear myoplasm. The atrophying liver of thyrotoxic rabbits also developed large increases in cathepsin D activity, but in this organ the increase was correlated with an increased number of cathepsin-D-positive secondary lysosomes without diffuse extralysosomal deposits. These observations indicate that changes in lysosomes and lysosomal enzyme activities elicited by thyrotoxicosis are tissue-specific. In some organs, the changes may be associated with net changes in protein balance or with tissue injury, but the exact functional significance of the lysosomal alterations remains uncertain.