Transthyretin uptake in placental cells is regulated by the high-density lipoprotein receptor, scavenger receptor class B member 1

Transfer of thyroid hormone into cells is critical for normal physiology and transplacental transfer of maternal thyroid hormones is essential for normal fetal growth and development. Free thyroid hormone is known to enter cells through specific cell surface transport proteins, and for many years this uptake of unbound thyroid hormones was assumed to be the only relevant mechanism. Recently, evidence has emerged of alternate pathways for hormone entry into cells that are dependent on hormone binding proteins. In this study we identify the high-density lipoprotein receptor Scavenger Receptor class B member 1 (SR-B1) as important in the uptake and transport of transthyretin-bound thyroid hormone by placental trophoblast cells. High-density lipoprotein increases expression of SR-B1 in placental cells but also reduces uptake of transthyretin-thyroid hormone through the SR-B1 transporter. SR-B1 is expressed in many cells and this study suggests that SR-B1 may be universally important in thyroid hormone uptake. Further investigation of SR-B1-TTR interactions may fundamentally change our understanding of hormone biology and have important clinical consequences.