Thyroid Hormone Transporters

Endocr Rev. 2020 Apr 1;41(2):bnz008. doi: 10.1210/endrev/bnz008.

Abstract

Thyroid hormone transporters at the plasma membrane govern intracellular bioavailability of thyroid hormone. Monocarboxylate transporter (MCT) 8 and MCT10, organic anion transporting polypeptide (OATP) 1C1, and SLC17A4 are currently known as transporters displaying the highest specificity toward thyroid hormones. Structure-function studies using homology modeling and mutational screens have led to better understanding of the molecular basis of thyroid hormone transport. Mutations in MCT8 and in OATP1C1 have been associated with clinical disorders. Different animal models have provided insight into the functional role of thyroid hormone transporters, in particular MCT8. Different treatment strategies for MCT8 deficiency have been explored, of which thyroid hormone analogue therapy is currently applied in patients. Future studies may reveal the identity of as-yet-undiscovered thyroid hormone transporters. Complementary studies employing animal and human models will provide further insight into the role of transporters in health and disease. (Endocrine Reviews 41: 1 - 55, 2020).

Keywords: AHDS; Allan-Herndon-Dudley syndrome; MCT8; MCT8 deficiency; OATP1C1; thyroid hormone; thyroid hormone transport; thyroid hormone transporters.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Transport / physiology*
  • Humans
  • Membrane Transport Proteins / deficiency
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / physiology*
  • Mental Retardation, X-Linked* / genetics
  • Mental Retardation, X-Linked* / metabolism
  • Mental Retardation, X-Linked* / physiopathology
  • Mental Retardation, X-Linked* / therapy
  • Monocarboxylic Acid Transporters / deficiency
  • Monocarboxylic Acid Transporters / genetics
  • Monocarboxylic Acid Transporters / physiology*
  • Muscle Hypotonia* / genetics
  • Muscle Hypotonia* / metabolism
  • Muscle Hypotonia* / physiopathology
  • Muscle Hypotonia* / therapy
  • Muscular Atrophy* / genetics
  • Muscular Atrophy* / metabolism
  • Muscular Atrophy* / physiopathology
  • Muscular Atrophy* / therapy
  • Organic Anion Transporters / deficiency
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / physiology*
  • Symporters / deficiency
  • Symporters / genetics
  • Symporters / physiology*
  • Thyroid Hormones / metabolism*
  • Thyroid Hormones / therapeutic use

Substances

  • Membrane Transport Proteins
  • Monocarboxylic Acid Transporters
  • Organic Anion Transporters
  • SLC16A2 protein, human
  • SLCO1C1 protein, human
  • Symporters
  • Thyroid Hormones

Supplementary concepts

  • Allan-Herndon-Dudley syndrome