The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Transthyretin uptake by the high-density lipoprotein receptor, scavenger receptor class B type 1. (#189)

Kerry Richard 1 2 3 , Kelly A Landers 1 , Michael C d'Emden 1 3 4
  1. Pathology Queensland, Queensland Health, Herston, Queensland, Australia
  2. Queensland University of Technology, Brisbane, Qld, Australia
  3. University of Queensland, Herston, Queensland, Australia
  4. Endocrinology and Diabetes, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia

Transfer of thyroid hormone into cells is critical for normal physiology. 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. In the last few years, substantial evidence has emerged of alternate pathways for hormone entry into cells that are dependent on hormone binding proteins. We have recently identified and demonstrated that the high-density lipoprotein receptor Scavenger Receptor class B type 1 (SR-B1) plays a role in the uptake and transport of the thyroid hormone binding protein transthyretin and transthyretin-thyroxine by placental trophoblast cells (1). High-density lipoprotein increases expression of SR-B1 in placental cells but also reduces uptake of transthyretin-thyroxine through the SR-B1 transporter. SR-B1 is expressed in many cells and this study suggests that it may be universally important in transthyretin and thyroid hormone uptake. Transthyretin is expressed and secreted into the serum by liver. Transthyretin and transthyretin-thyroxine have previously been shown to be taken up by primary hepatocytes via a previously unidentified receptor (2). Cholesterol is carried from peripheral tissues by HDL and taken up by hepatocytes through SR-B1. Our preliminary data suggest that SR-B1 plays a role in hepatic uptake of transthyretin (± thyroxine) and that HDL competes with transthyretin for uptake through hepatocyte SR-B1. Further investigation of SR-B1-transthyretin interactions may fundamentally change our understanding of hormone transport and biology.

  1. Landers KA, Li H, Mortimer RH, McLeod DSA, d'Emden MC, Richard K. Transthyretin uptake in placental cells is regulated by the high-density lipoprotein receptor, scavenger receptor class B member 1. Mol Cell Endocrinol. 2018.
  2. Sousa MM, Saraiva MJ. Internalization of transthyretin. Evidence of a novel yet unidentified receptor-associated protein (RAP)-sensitive receptor. J Biol Chem. 2001;276(17):14420-5.