Klein I
Department of Medicine, North Shore University Hospital, Manhasset, New York 11030.
Endocrinology. 1988 Jul;123(1):203-10. doi: 10.1210/endo-123-1-203.
To investigate the mechanism of thyroid hormone-induced cardiac hypertrophy, we have studied the in vivo changes in cardiac size and total myocardial content of both membrane and cytoskeletal enzymes in the rat after the administration of excess thyroid hormone. In response to 50 micrograms T4/day, there is a significant increase in heart rate and heart work associated with an increase in total heart size and protein content. Measurements of the specific activity of Na,K-ATPase and p-nitrophenol phosphatase demonstrate a small but significant increase in specific activity, while the specific activity of myosin ATPase is unchanged. To further probe the mechanism for T4-mediated hypertrophy we studied the in vivo effects of beta-adrenergic blockade on rat heart size. When animals were treated with both T4 and propranolol (10 mg/animal.day) cardiac hypertrophy was prevented. Propranolol alone at this dose did not affect heart rate, heart weight, or serum levels of T4 and T3. The present data suggest that 1) the hypertrophic response of the myocardium to excess thyroid hormone involves cytoplasmic as well as membrane proteins, 2) the increase in total myocardial protein, which can be blocked by propranolol, is indirectly mediated by increases in cardiac work rather than a direct effect of thyroid hormone.
为了研究甲状腺激素诱导心脏肥大的机制，我们研究了给大鼠过量注射甲状腺激素后心脏大小以及心肌膜酶和细胞骨架酶总含量的体内变化。每天注射50微克甲状腺素（T4）后，心率和心脏做功显著增加，同时心脏总体大小和蛋白质含量也增加。对钠钾ATP酶和对硝基苯酚磷酸酶比活性的测量表明，比活性有小幅但显著的增加，而肌球蛋白ATP酶的比活性没有变化。为了进一步探究T4介导的肥大机制，我们研究了β-肾上腺素能阻滞剂对大鼠心脏大小的体内影响。当动物同时接受T4和普萘洛尔（10毫克/动物·天）治疗时，心脏肥大得到预防。单独使用此剂量的普萘洛尔不影响心率、心脏重量或T4和T3的血清水平。目前的数据表明：1）心肌对过量甲状腺激素的肥大反应涉及细胞质蛋白和膜蛋白；2）心肌总蛋白的增加可被普萘洛尔阻断，它是由心脏做功增加间接介导的，而非甲状腺激素的直接作用。
