Landers Kelly A, d'Emden Michael C, Richard Kerry
Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland, Queensland Health, Herston, QLD 4029, Australia.
Department of Endocrinology and Diabetes, Royal Brisbane and Women's Hospital, Herston, QLD 4029, Australia.
J Lipids. 2019 Jun 18;2019:7317639. doi: 10.1155/2019/7317639. eCollection 2019.
Thyroid hormone (thyroxine, T4) is essential for the normal function of all cell types and is carried in serum bound to several proteins including transthyretin. Recently, evidence has emerged of alternate pathways for hormone entry into cells that are dependent on hormone binding proteins. Transthyretin and transthyretin bound T4 are endocytosed by placental trophoblasts through the high-density lipoprotein receptor, Scavenger Receptor Class B Type 1 (SR-B1). High density lipoprotein (HDL) affects the expression and function of SR-B1 in trophoblast cells. SR-B1 is also expressed in hepatocytes and we sought to determine if hepatocyte SR-B1 was involved in transthyretin or transthyretin-T4 uptake and whether uptake was affected by HDL. Transthyretin and transthyretin-T4 uptake by hepatocytes is not dependent on SR-B1. HDL treatment reduced SR-B1 expression. However, pretreatment of hepatocytes with HDL increased uptake of transthyretin-T4. Knockdown of SR-B1 expression using siRNA also increased transthyretin-T4 uptake. Coaddition of HDL to transthyretin uptake experiments blocked both transthyretin and transthyretin-T4 uptake. Hepatocyte uptake of transthyretin-T4 uptake is influenced by, but is not dependent on, SR-B1 expression. HDL also decreases transthyretin-T4 uptake and therefore diet or drugs may interfere with this process. This suggests that multiple lipoprotein receptors may be involved in the regulation of uptake of transthyretin-T4 in a cell-type specific manner. Further study is required to understand this important process.
甲状腺激素（甲状腺素，T4）对所有细胞类型的正常功能至关重要，且在血清中与包括甲状腺素转运蛋白在内的多种蛋白质结合运输。最近，有证据表明存在依赖激素结合蛋白的激素进入细胞的替代途径。甲状腺素转运蛋白以及与之结合的T4通过高密度脂蛋白受体，即B1型清道夫受体（SR-B1），被胎盘滋养层细胞内吞。高密度脂蛋白（HDL）影响滋养层细胞中SR-B1的表达和功能。SR-B1也在肝细胞中表达，我们试图确定肝细胞SR-B1是否参与甲状腺素转运蛋白或甲状腺素转运蛋白-T4的摄取，以及摄取是否受HDL影响。肝细胞对甲状腺素转运蛋白和甲状腺素转运蛋白-T4的摄取不依赖于SR-B1。HDL处理降低了SR-B1的表达。然而，用HDL预处理肝细胞会增加甲状腺素转运蛋白-T4的摄取。使用小干扰RNA敲低SR-B1的表达也会增加甲状腺素转运蛋白-T4的摄取。在甲状腺素摄取实验中同时添加HDL会阻断甲状腺素和甲状腺素转运蛋白-T4的摄取。肝细胞对甲状腺素转运蛋白-T4的摄取受SR-B1表达的影响，但不依赖于SR-B1表达。HDL也会降低甲状腺素转运蛋白-T4的摄取，因此饮食或药物可能会干扰这一过程。这表明多种脂蛋白受体可能以细胞类型特异性的方式参与甲状腺素转运蛋白-T4摄取的调节。需要进一步研究以了解这一重要过程。
