Lechan R M, Qi Y, Berrodin T J, Davis K D, Schwartz H L, Strait K A, Oppenheimer J H, Lazar M A
Division of Endocrinology, Metabolism, Molecular Medicine and Diabetes, New England Medical Center Hospitals, Boston, Massachussets 02111.
Endocrinology. 1993 Jun;132(6):2461-9. doi: 10.1210/endo.132.6.7684976.
The thyroid hormone receptors (TR) are nuclear proteins that include TR alpha and TR beta subtypes, each encoded by a separate gene. Both TR alpha and TR beta give rise to several isoforms of which three, TR alpha 1, TR beta 1, and TR beta 2 bind T3 and mediate the action of thyroid hormone. Although TR beta 2 was initially thought to be confined to the anterior pituitary, we recently observed small quantities of TR beta 2 messenger RNA (mRNA) by polymerase chain reaction analysis of discrete hypothalamic regions. To further examine the distribution of TR beta 2 in the brain, we performed immunocytochemical studies using a highly specific antiserum to TR beta 2, raised against a unique amino acid sequence (TR beta 2[131-145]) that is not present in the other known TRs. This antiserum immunoprecipitated TR beta 2 but not TR alpha 1 or TR beta 1. Immunoreactive TR beta 2 was widely distributed throughout the brain and primarily localized to the cell nucleus. Particularly intense immunostaining was present in the cerebral cortex, cerebellum, and hypothalamus, including regions where TR beta 2 mRNA had not previously been identified. In addition, immunoprecipitation of nuclear extracts with anti-TR beta 2 reduced total T3 binding capacity by approximately 20%, suggesting that immunoreactive TR beta 2 comprises a substantial portion of the total content of nuclear thyroid hormone binding proteins. These studies demonstrate that immunoreactive TR beta 2 is more widely represented in the central nervous system than previously suspected and may play an important role in mediating the action of T3 in many different regions of the brain. The finding of TR beta 2-like material could be due to a disproportionately high ratio of the TR beta 2 translation product and its mRNA in certain regions of the brain, or could indicate the existence of a novel TR beta 2-related protein that is important for T3 binding.
甲状腺激素受体（TR）是核蛋白，包括TRα和TRβ亚型，它们分别由不同基因编码。TRα和TRβ都产生几种亚型，其中TRα1、TRβ1和TRβ2这三种亚型能结合T3并介导甲状腺激素的作用。尽管TRβ2最初被认为仅存在于垂体前叶，但我们最近通过对离散下丘脑区域进行聚合酶链反应分析，观察到了少量的TRβ2信使核糖核酸（mRNA）。为了进一步研究TRβ2在脑中的分布，我们使用针对TRβ2的高特异性抗血清进行免疫细胞化学研究，该抗血清是针对一个其他已知TR中不存在的独特氨基酸序列（TRβ2[131 - 145]）制备的。这种抗血清能免疫沉淀TRβ2，但不能沉淀TRα1或TRβ1。免疫反应性TRβ2广泛分布于整个大脑，主要定位于细胞核。在大脑皮层、小脑和下丘脑，包括之前未发现TRβ2 mRNA的区域，都有特别强烈的免疫染色。此外，用抗TRβ2对核提取物进行免疫沉淀可使总T3结合能力降低约20%，这表明免疫反应性TRβ2占核甲状腺激素结合蛋白总含量的很大一部分。这些研究表明，免疫反应性TRβ2在中枢神经系统中的表达比之前怀疑的更为广泛，可能在介导T3在大脑许多不同区域的作用中发挥重要作用。发现TRβ2样物质可能是由于大脑某些区域中TRβ2翻译产物与其mRNA的比例过高，或者可能表明存在一种对T3结合很重要的新型TRβ2相关蛋白。
