Thyroid hormone is essential for the normal function of cells and is transported in serum bound to several proteins including transthyretin. For many years, it was thought that only free hormone could be transported into cells however, there is now evidence that hormone binding protein dependent uptake mechanisms also exist. Our recent study showed that transthyretin and transthyretin bound to thyroxine (T4) are endocytosed by placental trophoblasts through the high-density lipoprotein receptor, Scavenger Receptor Class B Type 1 (SR-B1) [1].
The liver plays an important role in the transport, metabolism and excretion of thyroid hormones and is an important site of hormone activity. 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 high density lipoprotein.
Transthyretin and transthyretin-T4 uptake by hepatocytes is not dependent on SR-B1. Knockdown of SR-B1 expression using siRNA resulted in increased transthyretin-T4 uptake and had no significant effect on transthyretin uptake. High density lipoprotein treatment of hepatocytes decreased SR-B1 expression in hepatocytes but increased uptake of transthyretin-T4. Addition of HDL to uptake experiments blocked both transthyretin and transthyretin-T4 uptake.
Hepatocyte uptake of transthyretin-T4 is not dependent on SR-B1 expression but is affected by SR-B1 levels. HDL also decreases both transthyretin and transthyretin-T4 uptake. This suggests that multiple lipoprotein receptors may be involved in the regulation of uptake of transthyretin-T4 in different cell types. Further study is required to identify the specific transporters involved.