Photoaffinity labeling of thyroid hormone receptors.
Photoaffinity labeling of thyroid hormone receptors.
复制标题
甲状腺激素受体的光亲和标记。
DOI：
10.1016/0163-7258(87)90069-6
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发表时间：
1987
影响因子：
13.5
通讯作者：
Samuels,HH
中科院分区：
文献类型：
--
作者：
Horowitz,ZD;Samuels,HH
甲状腺激素影响大多数动物种属的基本上所有组织的生长、发育和代谢（Oppenheimer，1983; Samuels，1983; Wolff and Wolff，1964）。在完整动物和培养细胞中的研究表明，3，5，3 '5'-四碘-L-甲状腺原氨酸（L-甲状腺素，L-T4）和3，5，3 '-三碘-L-甲状腺原氨酸（L-triiodothyronine，L-T3）通过刺激编码特定蛋白质的mRNA的积累来调节特定基因。这些基因中的几个的调节已经被详细研究。这些包括：在体内刺激大鼠垂体前叶中的生长激素合成（赫尔瓦斯等人，1975），在培养的大鼠垂体细胞中刺激生长激素基因表达（Dobner等，1981年; Evans等人，1982; Martial等人，1977; Samuels和Shapiro，1976; Samuels等人，1979 a，B; Seo等人，1977; Shapiro等人，1978; Spindler等人，1982，Yaffe和Samuels，1984），苹果酸酶mRNA的刺激（Magnuson和Nikodem，1983; Siddiqui等，1981; Towle等人，1981），以及编码具有未知功能的肝蛋白的几种其它基因（卡尔等人，1984年）。大量证据表明，在完整动物（Oppenheimer，1983）和培养细胞（Samuels，1983）中，基本上所有对甲状腺激素的细胞反应均由核相关受体介导。已显示几种产生生长激素的大鼠垂体细胞（GH-、GH 3和GC）的克隆株是用于研究甲状腺激素作用的极好模型（Evans等人，1982; Martial等人，1977; Samuels和Shapiro，1976; Samuels等人，1979 a，B; Seo等人，1977; Shapiro等人，1978; Spindler等人，1982年; Yaffe和Samuels，1984年）。在这些细胞中，生理浓度的L-T3和L-T4刺激生长激素mRNA积累（Martial等人，1977; Samuels等人，1979 a; Seo等人，1977; Shapiro等人，1978），其刺激动力学类似于激素给药后在垂体前叶中描述的（赫尔瓦斯等人，1975; Martial等人，1977; Samuels等人，1976年，1979年a）。完整细胞中甲状腺激素受体的光亲和标记研究提供了关于受体异质性和结构的有趣信息（Casanova et al.，1984; Pascual等人，1982年）。用N-2-重氮-3，3，3-三氟丙酰基-L-三碘甲状腺原氨酸（L-T3-PAL）进行这些研究。在完整的GH~+细胞中使用该探针的研究已经鉴定了丰富的47，000分子量（Mr）的种类（总受体的75%）和较不丰富的57，000 Mr双联体形式（约受体的25%）。这两种受体形式对多种甲状腺激素类似物表现出相同的亲和力。这一观察结果，沿着两种Mr光亲和标记的物质与金黄色葡萄球菌V8蛋白酶产生相同大小的12 SI-肽片段的事实，表明受体形式的配体结合结构域即使不相同也是非常相似的（Casanova等人，1984年）。在这篇综述中，我们讨论了最近的研究已经检查了其他t25碘-甲状腺原氨酸光亲和标记探针的效用。这些包括L-T4-PAL和3，3 ′ 5 ′-三碘-L-甲状腺原氨酸的光亲和标记衍生物（L-reverseT 3，L-
The thyroid hormones affect the growth, development, and metabolism of essentially all tissues of most animal species (Oppenheimer, 1983; Samuels, 1983; Wolff and Wolff, 1964). Studies in intact animals and in cultured cells indicate that 3, 5, 3'5'-tetraiodo-L-thyronine (L-thyroxine, L-T4) and 3, 5, 3'-triiodo-L-thyronine (L-triiodothyronine, L-T3) regulate specific genes by stimulating the accumulation of mRNAs which code for specific proteins. The regulation of several of these genes has been studied in detail. These include: the stimulation of growth hormone synthesis in rat anterior pituitary in vivo (Hervas et al., 1975), stimulation of growth hormone gene expression in cultured rat pituitary cells (Dobner et al., 1981; Evans et al., 1982; Martial et al., 1977; Samuels and Shapiro, 1976; Samuels et al., 1979a, b; Seo et al., 1977; Shapiro et al., 1978; Spindler et al., 1982, Yaffe and Samuels, 1984), stimuation of malic enzyme mRNA (Magnuson and Nikodem, 1983; Siddiqui et al., 1981; Towle et al., 1981), as well as several other genes which encode for hepatic proteins with unknown functions (Carr et al., 1984). Abundant evidence indicates that essentially all cellular responses to thyroid hormone in intact animals (Oppenheimer, 1983) and in cultured cells (Samuels, 1983) are mediated by a nuclear associated receptor. Several clonal strains of growth hormone producing rat pituitary cells (GH~, GH3, and GC) have been shown to be excellent models for the study of thyroid hormone action (Evans et al., 1982; Martial et al., 1977; Samuels and Shapiro, 1976; Samuels et al., 1979a, b; Seo et al., 1977; Shapiro et al., 1978; Spindler et al., 1982; Yaffe and Samuels, 1984). In these cells physiologic concentrations of L-T3 and L-T4 stimulate growth hormone mRNA accumulation (Martial et al., 1977; Samuels et al., 1979a; Seo et al., 1977; Shapiro et al., 1978) with kinetics of stimulation similar to that described in anterior pituitary after hormone administration (Hervas et al., 1975; Martial et al., 1977; Samuels et al., 1976, 1979a). These pituitary cell lines have proved to be extremely useful in analyzing the structure and properties of the thyroid hormone nuclear receptor.Photoaffinity labeling studies of the thyroid hormone receptor in intact cells have provided interesting information concerning receptor heterogeneity and structure (Casanova et al., 1984; Pascual et al., 1982). These studies were performed with N-2-diazo-3, 3, 3-trifluoropropionyl-L-triiodothyronine (L-T3-PAL). Studies using this probe in intact GH~ cells have identified an abundant 47,000 molecular weight (Mr) species (75% of total receptor) and a less abundant 57,000 Mr doublet form (approximately 25% of receptor). The two receptor forms show identical affinities for a variety of thyroid hormone analogues. This observation, along with the fact that both Mr photoaffinity labeled species generate identical size 12SI-peptide fragments with Staphylococcal aureus V8 protease, suggest that the ligand binding domain of the receptor forms are very similar, if not identical (Casanova et al., 1984). In this review we discuss more recent studies which have examined the utility of other t25I-iodothyronine photoaffinity labeling probes. These include L-T4-PAL and a photoaffinity labeled derivative of 3, 3'5'-triiodo-L-thyronine (L-reverseT3, L-