Hupart K H, Hodin R A, Lazar M A, Shapiro L E, Chin W W, Surks M I
Department of Medicine, Montefiore Medical Center, Bronx, New York.
Thyroid. 1993 Spring;3(1):55-8. doi: 10.1089/thy.1993.3.55.
In the rat tumor model of the sick euthyroid syndrome, differential regulation of T3-induced cellular responses have been demonstrated in liver and anterior pituitary. These effects occur with a concomitant decrease in nuclear thyroid hormone receptor (TR) number as measured by the binding of 125I-labeled T3. To explore the possibility that these altered responses to T3 in tumor rats resulted from changes in the expression of different TR forms, we correlated the relative abundance of mRNAs encoding each receptor form with the concentration of TR measured by specific T3 binding. In anterior pituitary of tumor rats, TR beta-1 and beta-2 mRNA levels decreased to 51 and 45%, respectively, compared to controls; rat c-erb A alpha-2 mRNA, which encodes a TR-related DNA alpha-binding protein that does not bind T3, decreased to 46% of control. These findings correlate with a decrease in nuclear T3 binding capacity that has been shown to be 63% of control. The level of TR beta-1 mRNA, the only quantifiable TR form in liver, was decreased to 61% of control in the same hepatic tissue that revealed a 50% decrease in TR as measured by specific T3 binding. The coordinate down-regulation of all TR mRNA forms to a degree that parallels the decrease in TR number as measured by specific T3 binding suggests that the differential regulation of T3-mediated effects in illness is by a mechanism other than changing concentrations of specific receptor forms.(ABSTRACT TRUNCATED AT 250 WORDS)
在病态甲状腺综合征的大鼠肿瘤模型中，已证实在肝脏和垂体前叶中，T3诱导的细胞反应存在差异调节。这些效应伴随着核甲状腺激素受体（TR）数量的减少，这是通过125I标记的T3结合来测量的。为了探究肿瘤大鼠对T3的这些改变的反应是否是由不同TR形式表达的变化引起的，我们将编码每种受体形式的mRNA的相对丰度与通过特异性T3结合测量的TR浓度进行了关联。与对照组相比，肿瘤大鼠垂体前叶中TRβ-1和β-2 mRNA水平分别降至51%和45%；大鼠c-erb Aα-2 mRNA，其编码一种不结合T3的TR相关DNAα结合蛋白，降至对照组的46%。这些发现与核T3结合能力的降低相关，核T3结合能力已被证明是对照组的63%。TRβ-1 mRNA水平是肝脏中唯一可定量的TR形式，在同一肝组织中降至对照组的61%，通过特异性T3结合测量显示该肝组织中TR减少了50%。所有TR mRNA形式的协同下调程度与通过特异性T3结合测量的TR数量减少程度平行，这表明疾病中T3介导效应的差异调节是通过改变特定受体形式浓度以外的机制实现的。（摘要截断于250字）
