Thyroid hormones and their effects: a new perspective
Thyroid hormones and their effects: a new perspective
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DOI：
10.1111/j.1469-185x.2000.tb00054.x
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发表时间：
2000-11
影响因子：
10
通讯作者：
A. Hulbert
中科院分区：
文献类型：
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作者：
A. Hulbert
甲状腺激素具有很强的疏水性，具有生物活性的激素有 3',5',3,5-L-四碘甲状腺原氨酸 (T4)、3',5,3-L-三碘甲状腺原氨酸 (T3)、3',5',3-L-三碘甲状腺原氨酸 (rT3) 和 3,5,-L-二碘甲状腺原氨酸 (3,5-T2)。在生理 pH 值下，这些碘甲状腺原氨酸的酚 OH 基团的解离是其物理化学的重要决定因素，影响其生物效应。当非离子化时，这些碘甲状腺原氨酸具有强两亲性。有人提出，碘甲腺原氨酸是脊椎动物生物膜的正常成分。在成年脊椎动物的血浆中，未结合的 T4 和 T3 在皮摩尔范围内调节，而蛋白质结合的 T4 和 T3 则维持在纳摩尔范围内。甲状腺激素结合血浆蛋白的功能是确保其在全身均匀分布。脊椎动物中三种类型的膜结合细胞脱碘酶系统产生各种碘甲状腺原氨酸。脱碘酶的分布在组织之间有所不同，并且每种脱碘酶都有不同的发育特征。甲状腺激素对脊椎动物有多种作用。据认为这些激素有几种作用模式。（1）核受体模式在控制这些激素的血浆和细胞水平的甲状腺激素轴中特别重要。（2）这些激素与组织中的膜密切相关，通常使这些膜硬化。（3）它们还影响膜双层的酰基组成，这表明这是由于细胞对甲状腺激素诱导的膜硬化做出了反应。它们对膜物理状态的直接影响以及随后膜成分的变化会导致其他几种甲状腺激素效应。对代谢的影响可能主要是由于膜酰基的变化。甲状腺激素还有其他涉及膜受体的作用，并影响细胞与细胞外基质的相互作用。对甲状腺激素的作用进行了回顾，发现它似乎是这些不同作用模式的组合。在发育过程中，脊椎动物表现出 T4 和其他甲状腺激素的激增，以及脱碘酶和核受体的外观特征。使用类似物的证据支持多种作用模式。对 20 世纪 60 年代初数据的重新检验支持了膜作用。受体“敲除”小鼠的研究结果支持受体在甲状腺轴发育中的重要作用。与传统的激素信使相比，这些碘甲状腺原氨酸可能更适合被视为“维生素”类分子。
The thyroid hormones are very hydrophobic and those that exhibit biological activity are 3′,5′,3,5‐Ltetraiodothyronine (T4), 3′,5,3‐L‐triiodothyronine (T3), 3′,5′,3‐L‐triiodothyronine (rT3) and 3,5,‐Ldiiodothyronine (3,5‐T2). At physiological pH, dissociation of the phenolic ‐OH group of these iodothyronines is an important determinant of their physical chemistry that impacts on their biological effects. When non‐ionized these iodothyronines are strongly amphipathic. It is proposed that iodothyronines are normal constituents of biological membranes in vertebrates. In plasma of adult vertebrates, unbound T4 and T3 are regulated in the picomolar range whilst protein‐bound T4 and T3 are maintained in the nanomolar range. The function of thyroid‐hormone‐binding plasma proteins is to ensure an even distribution throughout the body. Various iodothyronines are produced by three types of membrane‐bound cellular deiodinase enzyme systems in vertebrates. The distribution of deiodinases varies between tissues and each has a distinct developmental profile. Thyroid hormones have many effects in vertebrates. It is proposed that there are several modes of action of these hormones.(1) The nuclear receptor mode is especially important in the thyroid hormone axis that controls plasma and cellular levels of these hormones.(2) These hormones are strongly associated with membranes in tissues and normally rigidify these membranes.(3) They also affect the acyl composition of membrane bilayers and it is suggested that this is due to the cells responding to thyroid‐hormone‐induced membrane rigidification. Both their immediate effects on the physical state of membranes and the consequent changes in membrane composition result in several other thyroid hormone effects. Effects on metabolism may be due primarily to membrane acyl changes. There are other actions of thyroid hormones involving membrane receptors and influences on cellular interactions with the extracellular matrix. The effects of thyroid hormones are reviewed and appear to be combinations of these various modes of action. During development, vertebrates show a surge in T4 and other thyroid hormones, as well as distinctive profiles in the appearance of the deiodinase enzymes and nuclear receptors. Evidence from the use of analogues supports multiple modes of action. Re‐examination of data from the early 1960s supports a membrane action. Findings from receptor ‘knockout’ mice supports an important role for receptors in the development of the thyroid axis. These iodothyronines may be better thought of as ‘vitamone’ ‐like molecules than traditional hormonal messengers.