Dickson P W, Aldred A R, Menting J G, Marley P D, Sawyer W H, Schreiber G
Russell Grimwade School of Biochemistry, University of Melbourne, Parkville, Victoria, Australia.
J Biol Chem. 1987 Oct 15;262(29):13907-15.
The role of the choroid plexus in thyroid hormone transport between body and brain, suggested by strong synthesis and secretion of transthyretin in this tissue, was investigated in in vitro and in vivo systems. Rat choroid plexus pieces incubated in vitro were found to accumulate thyroid hormones from surrounding medium in a non-saturable process. At equilibrium, the ratio of thyroid hormone concentration in choroid plexus pieces to that in medium decreased upon increasing the concentration of transthyretin in the medium. Fluorescence quenching of fluorophores located at different depths in liposome membranes showed maximal hormone accumulation in the middle of the phospholipid bilayer. Partition coefficients of thyroxine and triiodothyronine between lipid and aqueous phase were about 20,000. After intravenous injection of 125I-labeled thyroid hormones, choroid plexus and parts of the brain steadily accumulated 125I-thyroxine, but not [125I]triiodothyronine, for many hours. The accumulation of 125I-thyroxine in choroid plexus preceded that in brain. The amount of 125I-thyroxine in non-brain tissues and the [125I]triiodothyronine content of all tissues decreased steadily beginning immediately after injection. A model is proposed for thyroxine transport from the bloodstream into cerebrospinal fluid based on partitioning of thyroxine between choroid plexus and surrounding fluids and binding of thyroxine to transthyretin newly synthesized and secreted by choroid plexus.
鉴于脉络丛中甲状腺素转运蛋白的强烈合成和分泌,人们在体外和体内系统中研究了脉络丛在身体与大脑之间甲状腺激素转运中的作用。体外培养的大鼠脉络丛碎片能够以非饱和过程从周围培养基中积累甲状腺激素。达到平衡时,培养基中甲状腺素转运蛋白浓度增加,脉络丛碎片中甲状腺激素浓度与培养基中甲状腺激素浓度的比值降低。脂质体膜不同深度处荧光团的荧光猝灭显示,激素在磷脂双分子层中间积累最多。甲状腺素和三碘甲状腺原氨酸在脂质相和水相之间的分配系数约为20000。静脉注射125I标记的甲状腺激素后,脉络丛和部分脑区在数小时内持续积累125I-甲状腺素,但不积累[125I]三碘甲状腺原氨酸。脉络丛中125I-甲状腺素的积累先于脑内。注射后,非脑组织中125I-甲状腺素的量以及所有组织中[125I]三碘甲状腺原氨酸的含量立即开始稳步下降。基于甲状腺素在脉络丛与周围液体之间的分配以及甲状腺素与脉络丛新合成和分泌的甲状腺素转运蛋白的结合,提出了一个甲状腺素从血液转运到脑脊液的模型。