Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin , Germany.
Institut für Biochemie und Molekularbiologie, Rheinische Friedrich-Wilhelms-Universität Bonn , Bonn , Germany.
Front Endocrinol (Lausanne). 2014 Jun 24;5:98. doi: 10.3389/fendo.2014.00098. eCollection 2014.
Thyroid hormone (TH) transport into the brain is not only pivotal for development and differentiation, but also for maintenance and regulation of adult central nervous system (CNS) function. In this review, we highlight some key factors and structures regulating TH uptake and distribution. Serum TH binding proteins play a major role for the availability of TH since only free hormone concentrations may dictate cellular uptake. One of these proteins, transthyretin is also present in the cerebrospinal fluid (CSF) after being secreted by the choroid plexus. Entry routes into the brain like the blood-brain-barrier (BBB) and the blood-CSF-barrier will be explicated regarding fetal and adult status. Recently identified TH transmembrane transporters (THTT) like monocarboxylate transporter 8 (Mct8) play a major role in uptake of TH across the BBB but as well in transport between cells like astrocytes and neurons within the brain. Species differences in transporter expression will be presented and interference of TH transport by endogenous and exogenous compounds including endocrine disruptors and drugs will be discussed.
甲状腺激素 (TH) 向大脑的转运不仅对发育和分化至关重要,而且对成年中枢神经系统 (CNS) 功能的维持和调节也至关重要。在这篇综述中,我们强调了一些调节 TH 摄取和分布的关键因素和结构。血清 TH 结合蛋白在 TH 的可用性中起主要作用,因为只有游离激素浓度才能决定细胞摄取。这些蛋白质之一,转甲状腺素蛋白在脉络丛分泌后也存在于脑脊液 (CSF) 中。将详细阐述进入大脑的途径,如血脑屏障 (BBB) 和血脑脊液屏障,分别针对胎儿和成人的状态。最近发现的 TH 跨膜转运体 (THTT),如单羧酸转运蛋白 8 (Mct8),在 TH 通过 BBB 的摄取中起主要作用,但在脑内星形胶质细胞和神经元等细胞之间的运输中也起作用。将介绍不同物种在转运体表达上的差异,并讨论内源性和外源性化合物(包括内分泌干扰物和药物)对 TH 转运的干扰。