Yoshinari M, Inoue K, Nakashima T, Okamura K, Shiroozu A, Nishitani H, Omae T, Torisu M, Noguchi S
Metabolism. 1983 Apr;32(4):348-54. doi: 10.1016/0026-0495(83)90042-2.
Although the activity of lysosomal protease in Graves' thyroid is considered to be increased, there has been no quantitative method to estimate the protease activity in the thyroid tissue due to the contamination of thyroglobulin (Tg) which varies in susceptibility to the protease. In the present study, the proteolytic activity (PA) of thyroid lysosomal protease preparation (P25) separated from Tg was assayed using 125I labeled rat Tg. More than 95% of 125I-Tg was hydrolyzed at pH 4.0 without deiodination, and the pattern of liberated iodoamino acids resembled that of pronase digest except for a higher T3/T4 ratio. Thirty-seven Graves' thyroids and 15 paranodular thyroid tissues were assayed. PA, the specific PA (SPA; calculated as PA per mg P25 protein) and PA per DNA content in Graves' thyroids were significantly higher than those in controls. There were good correlations among PA, SPA and PA per DNA content of the thyroid tissue. PA and SPA in the thyroid from 29 patients with Graves' disease treated with propylthiouracil or methimazole did not correlate with serum thyroid hormone level immediately before surgery. In 8 patients treated with KI, PA from 5 patients whose serum thyroid hormone levels had been normalized were significantly lower than those from 3 patients who were still thyrotoxic.(ABSTRACT TRUNCATED AT 250 WORDS)
尽管Graves病甲状腺中溶酶体蛋白酶的活性被认为有所增加,但由于甲状腺球蛋白(Tg)对蛋白酶的敏感性不同而造成污染,一直没有定量方法来估计甲状腺组织中的蛋白酶活性。在本研究中,使用125I标记的大鼠Tg对从Tg中分离出的甲状腺溶酶体蛋白酶制剂(P25)的蛋白水解活性(PA)进行了测定。超过95%的125I-Tg在pH 4.0时被水解而未发生脱碘,释放的碘氨基酸模式与链霉蛋白酶消化的模式相似,只是T3/T4比值更高。对37个Graves病甲状腺组织和15个结节旁甲状腺组织进行了测定。Graves病甲状腺组织中的PA、比PA(SPA;以每毫克P25蛋白的PA计算)和每DNA含量的PA均显著高于对照组。甲状腺组织的PA、SPA和每DNA含量的PA之间存在良好的相关性。29例接受丙硫氧嘧啶或甲巯咪唑治疗的Graves病患者甲状腺中的PA和SPA与手术前即刻的血清甲状腺激素水平无关。在8例接受碘化钾治疗的患者中,5例血清甲状腺激素水平已恢复正常患者的PA显著低于3例仍有甲状腺毒症患者的PA。(摘要截短于250字)