Tibaldi J M, Surks M I
Endocr Rev. 1985 Winter;6(1):87-102. doi: 10.1210/edrv-6-1-87.
Rats bearing transplantable Walker 256 carcinoma provide an opportunity to assess thyroid function and activity during an interval of time when the tumor has not affected growth rate. Rats with tumor have decreased serum T4 and T3 concentration and decreased serum FT4 and FT3 as well. These changes are due to a decrease in binding of iodothyronines by the serum binding proteins, an increase in the fractional rate of T4 metabolism and a decrease in thyroidal secretion. The decrease in activity of the thyroid gland appears to be due to reduced sensitivity of the thyroid to circulating TSH. Despite decreased serum FT4 and FT3 concentrations, serum TSH remains normal, not increased as would be anticipated in a hypothyroidal animal. Nevertheless, a further experimental decrease in serum T4 and/ or T3 from the already reduced serum iodothyronine levels of the tumor bearing rat results in a normal increment in serum TSH. Thus, TSH secretion appears to be regulated normally despite decreased concentrations of pituitary nuclear T3. This finding suggests that tumor bearing rats have greater than normal sensitivity to T3 in their regulation of TSH secretion. Rats with Walker 256 carcinoma have decreased concentrations of hepatic nuclear T3 receptors and a decrease in T3 specifically bound to the receptors. The fractional occupancy of hepatic nuclear receptors appears relatively normal. The dose-response of alpha-GPD in relation to fractional nuclear T3 receptor occupancy appears shifted up and to the left in tumor bearing rats, whereas the curve for ME is shifted down to the right. The appearance rates of these enzymes are described by similar functions. These findings suggest that postreceptor factors in tumor bearing rats may result in augmentation of some and depression of other biologic responses to thyroid hormones. If the results of these studies are extended to sick patients, they may provide a possible mechanism whereby patients maintain the euthyroid clinical state despite a decrease in serum T3. Thus, postreceptor factors may enhance those thyroidal responses which characterize the euthyroid clinical state. Moreover, attenuation of other thyroidal responses related to conservation of protein may provide a distinct adaptive advantage to the patient with nonthyroidal illness with or without decreased food consumption.
携带可移植性Walker 256癌的大鼠提供了一个机会，可在肿瘤尚未影响生长速率的时间段内评估甲状腺功能和活性。患有肿瘤的大鼠血清T4和T3浓度降低，血清游离T4（FT4）和游离T3（FT3）也降低。这些变化是由于血清结合蛋白对碘甲状腺原氨酸的结合减少、T4代谢分数率增加以及甲状腺分泌减少所致。甲状腺活性降低似乎是由于甲状腺对循环促甲状腺激素（TSH）的敏感性降低。尽管血清FT4和FT3浓度降低，但血清TSH仍保持正常，并未像甲状腺功能减退动物那样升高。然而，将携带肿瘤大鼠已经降低的血清碘甲状腺原氨酸水平进一步实验性降低血清T4和/或T3，会导致血清TSH正常增加。因此，尽管垂体核T3浓度降低，但TSH分泌似乎仍受到正常调节。这一发现表明，携带肿瘤的大鼠在调节TSH分泌时对T3的敏感性高于正常水平。患有Walker 256癌的大鼠肝细胞核T3受体浓度降低，与受体特异性结合的T3减少。肝细胞核受体的占有率分数相对正常。在携带肿瘤的大鼠中，α-甘油磷酸脱氢酶（alpha-GPD）相对于核T3受体占有率分数的剂量反应曲线似乎向上和向左移动，而苹果酸酶（ME）的曲线向下和向右移动。这些酶的出现率由相似的函数描述。这些发现表明，携带肿瘤的大鼠中的受体后因素可能导致对甲状腺激素的某些生物学反应增强，而对其他反应则抑制。如果将这些研究结果推广到患病患者，它们可能提供一种可能的机制，据此患者尽管血清T3降低仍能维持甲状腺功能正常的临床状态。因此，受体后因素可能增强那些表征甲状腺功能正常临床状态的甲状腺反应。此外，与蛋白质保存相关的其他甲状腺反应的减弱可能为患有非甲状腺疾病的患者（无论是否减少食物摄入）提供明显的适应性优势。
