Cavalieri R R
Nuclear Medicine Service, VA Medical Center, San Francisco, California, USA.
Thyroid. 1997 Apr;7(2):177-81. doi: 10.1089/thy.1997.7.177.
Iodine plays a central role in thyroid physiology, being both a major constituent of thyroid hormones (THS) and a regulator of thyroid gland function. This review concerns those aspects of thyroid physiology in which significant advances have been made in recent years. We have known for decades that the thyroid gland concentrates iodine (I-) against an electrochemical gradient by a carrier-mediated mechanism driven by ATP. A similar I- uptake mechanism is found in other organs, including salivary glands, stomach, choroid plexus, and mammary glands, but only in the thyroid does TSH regulate the process. This past year saw a major advance with the cloning of the thyroid I- transporter. This development opens the way to an elucidation of the regulation of I- transport in the normal gland and in thyroid neoplasms that lack this property ("cold" nodules). All of the subsequent steps in TH biosynthesis, from oxidation and organification of iodide to the secretion of T4 and T3 into the circulation, are stimulated by TSH and inhibited by excess iodine. Recently, some of the regulatory mechanisms have been clarified. The function of the major TH-binding proteins in plasma is to maintain an equilibrium between extracellular and cellular hormone pools. Transthyretin, the principal T4-binding protein in cerebrospinal fluid, may play a similar role in the central nervous system. Although it generally is agreed that cellular uptake of TH is a function of the unbound (free) form of the hormone, there is evidence that certain TH-binding plasma proteins (i.e., apolipoproteins) may serve specific transport functions. The intracellular concentration of T3, the active TH, is determined by the rates of cellular uptake of T4 and T3, the rates of metabolic transformation, including conversion of T4 to T3, and the rate of T3 efflux. The latter has been assumed to be a passive process. However, recent studies by our group in San Francisco have shown that T3 is transported out of cells by a specific, saturable, verapamil-inhibitable mechanism. This T3 efflux system is widespread among cells from many tissues, and, at least in liver, modulates intracellular and nuclear concentration of the hormone and thereby influences TH action.
碘在甲状腺生理过程中起着核心作用，它既是甲状腺激素（THS）的主要成分，也是甲状腺功能的调节剂。本综述关注近年来甲状腺生理学中取得重大进展的那些方面。几十年来我们已经知道，甲状腺通过由ATP驱动的载体介导机制逆电化学梯度浓缩碘（I-）。在包括唾液腺、胃、脉络丛和乳腺在内的其他器官中也发现了类似的I-摄取机制，但只有在甲状腺中促甲状腺激素（TSH）才调节这一过程。过去一年，甲状腺I-转运体的克隆取得了重大进展。这一进展为阐明正常腺体和缺乏这种特性的甲状腺肿瘤（“冷”结节）中I-转运的调节开辟了道路。TH生物合成的所有后续步骤，从碘化物的氧化和有机化到T4和T3分泌到循环中，都受到TSH的刺激，并被过量碘抑制。最近，一些调节机制已经得到阐明。血浆中主要TH结合蛋白的功能是维持细胞外和细胞内激素池之间的平衡。转甲状腺素蛋白是脑脊液中主要的T4结合蛋白，可能在中枢神经系统中发挥类似作用。虽然人们普遍认为TH的细胞摄取是激素未结合（游离）形式的功能，但有证据表明某些TH结合血浆蛋白（即载脂蛋白）可能具有特定的转运功能。活性TH即T3的细胞内浓度取决于T4和T3的细胞摄取速率、代谢转化速率，包括T4转化为T3的速率以及T3流出速率。后者一直被认为是一个被动过程。然而，我们旧金山团队最近的研究表明，T3通过一种特定的、可饱和的、维拉帕米可抑制的机制从细胞中转运出来。这种T3流出系统在许多组织的细胞中广泛存在，并且至少在肝脏中，调节激素的细胞内和核浓度，从而影响TH的作用。
