Murayama-Oda K, Imamura K, Kim H K, Tanaka T
Department of Nutrition, Osaka University Medical School.
Jpn J Cancer Res. 1991 Jan;82(1):98-108. doi: 10.1111/j.1349-7006.1991.tb01752.x.
We examined the mechanism of abnormality of thyroid hormone metabolism in Walker 256 carcinosarcoma-bearing rats. The serum levels of thyroxine (T4), 3,5,3'-triiodothyronine (T3) and thyroid-stimulating hormone (TSH), and the responses of serum T4 and T3 to exogenous TSH in tumor-bearing rats on day 14 after inoculation of tumor cells were significantly less than those in pair-fed control (PFC) rats, suggesting that the metabolic abnormality of thyroid hormones may be caused by disorder of both peripheral and central functions, and that a certain tumor-derived factor may be involved in this abnormality. An active factor responsible for the metabolic abnormality was found in soluble cytosol fraction (SF) of the tumor cells. Administration of the SF to normal rats significantly reduced their serum T4 and T3 concentrations, liver 5'-deiodinase (5'-DI) activity, responsiveness of the thyroid gland to TSH and food intake compared with those of PFC rats, but, unlike the tumor, did not reduce the serum TSH level. This biologically active factor in the SF was found to be a heat-labile protein and specific to the tumor. It was tentatively named serum thyroid hormone reducing factor (STRF). STRF was partially purified from the SF by ammonium sulfate fractionation and DEAE-cellulose chromatography. Partially purified STRF preparation significantly diminished the serum T4 and T3 concentrations and liver 5'-DI activity and food intake of normal rats compared with those of PFC rats, mimicking the changes associated with the tumor in tumor-bearing animals. These results suggested that abnormality of thyroid hormone metabolism in tumor-bearing animals may partly be caused by STRF-mediated modulation at peripheral and thyroid gland levels. Whether STRF actually induces anorexia remains to be clarified.
我们研究了Walker 256癌肉瘤荷瘤大鼠甲状腺激素代谢异常的机制。接种肿瘤细胞后第14天，荷瘤大鼠血清甲状腺素（T4）、3,5,3'-三碘甲状腺原氨酸（T3）和促甲状腺激素（TSH）水平，以及血清T4和T3对外源性TSH的反应，均显著低于配对喂养对照（PFC）大鼠，提示甲状腺激素代谢异常可能是由外周和中枢功能紊乱引起的，且某种肿瘤衍生因子可能参与了这种异常。在肿瘤细胞的可溶性胞质部分（SF）中发现了一种导致代谢异常的活性因子。与PFC大鼠相比，给正常大鼠注射SF后，其血清T4和T3浓度、肝脏5'-脱碘酶（5'-DI）活性、甲状腺对TSH的反应性和食物摄入量均显著降低，但与肿瘤不同的是，血清TSH水平并未降低。SF中的这种生物活性因子被发现是一种热不稳定蛋白，且对肿瘤具有特异性。它被暂命名为血清甲状腺激素降低因子（STRF）。通过硫酸铵分级分离和DEAE-纤维素层析从SF中对STRF进行了部分纯化。与PFC大鼠相比，部分纯化的STRF制剂显著降低了正常大鼠的血清T4和T3浓度、肝脏5'-DI活性和食物摄入量，模拟了荷瘤动物中与肿瘤相关的变化。这些结果提示，荷瘤动物甲状腺激素代谢异常可能部分是由STRF在外周和甲状腺水平介导的调节所致。STRF是否真的会导致厌食仍有待阐明。
