DeMartino G N, Goldberg A L
Proc Natl Acad Sci U S A. 1978 Mar;75(3):1369-73. doi: 10.1073/pnas.75.3.1369.
Because protein degradation in liver and skeletal muscle is increased by thyroid hormones and decreased by thyroidectomy; we investigated the influence of thyroid hormones on the level of lysosomal enzymes. Hypophysectomized rats received daily injections of L-thyroxine or L-triiodothyronine. After 3 days of this regimen, homogenates of liver and skeletal muscle showed a 2- to 3-fold increase in the activities of cathepsin D, cathepsin B, and other lysosomal enzymes including leucine aminopeptidase, acid phosphatase, beta-galactosidase, N-acetylglucosaminidase, and alpha-mannosidase. In liver, this effect reflected increased enzyme activity in the two subcellular fractions that normally contain lysosomes. Titration of cathepsin D with pepstatin indicated that the increase in this activity resulted from an increase in the number of enzyme molecules. These effects occurred with both pharmacologic (thyrotoxic) and physiologic (growth-promoting) doses of thyroid hormones. Liver and skeletal muscle from thyroidectomized rats had approximately 50% of the normal levels of lysosomal enzyme activities. Under these various conditions, heart and kidney, tissues in which protein degradation does not appear to be influenced by thyroid hormones, showed no significant changes in lysosomal hydrolases. Thus, thyroid hormones regulate proteolytic and other lysosomal enzyme activities in those tissues in which these hormones influence protein degradation. Many characteristic features of hyperthyroidism and hypothyroidism may result from changes in levels of lysosomal enzymes.
由于甲状腺激素可增加肝脏和骨骼肌中的蛋白质降解，而甲状腺切除则可降低蛋白质降解；因此我们研究了甲状腺激素对溶酶体酶水平的影响。对垂体切除的大鼠每日注射L-甲状腺素或L-三碘甲状腺原氨酸。在这种给药方案持续3天后，肝脏和骨骼肌匀浆中组织蛋白酶D、组织蛋白酶B以及包括亮氨酸氨肽酶、酸性磷酸酶、β-半乳糖苷酶、N-乙酰葡糖胺酶和α-甘露糖苷酶在内的其他溶酶体酶的活性增加了2至3倍。在肝脏中，这种效应反映了正常情况下含有溶酶体的两个亚细胞组分中酶活性的增加。用胃酶抑素滴定组织蛋白酶D表明，该活性的增加是由于酶分子数量的增加。甲状腺激素的药理剂量（甲状腺毒症）和生理剂量（促进生长）均产生了这些效应。甲状腺切除大鼠的肝脏和骨骼肌中溶酶体酶活性约为正常水平的50%。在这些不同条件下，心脏和肾脏这两种蛋白质降解似乎不受甲状腺激素影响的组织，其溶酶体水解酶没有明显变化。因此，甲状腺激素在那些其蛋白质降解受这些激素影响的组织中调节蛋白水解和其他溶酶体酶活性。甲状腺功能亢进和甲状腺功能减退的许多特征可能是由溶酶体酶水平的变化引起的。
