Membrane receptor for thyroid hormone: Physiologic and pharmacologic implications

Paul J. Davis, Faith B. Davis, Shaker A. Mousa, Mary K. Luidens, Hung Yun Lin

Research output: Contribution to journalReview article

119 Citations (Scopus)

Abstract

Plasma membrane integrin αvβ3 is a cell surface receptor for thyroid hormone at which nongenomic actions are initiated. L-thyroxine (T 4) and 3,3′,5- triiodo-L-thyronine (T3) promote angiogenesis and tumor cell proliferation via the receptor. Tetraiodothyroacetic acid (tetrac), a deaminated T4 derivative, blocks the nongenomic proliferative and proangiogenic actions of T 4 andT 3. Acting at the integrin independently ofT 4 andT 3, tetrac and a novel nanoparticulate formulation of tetrac that acts exclusively at the cell surface have oncologically desirable antiproliferative actions on multiple tumor cell survival pathway genes. These agents also block the angiogenic activity of vascular growth factors. Volume and vascular support of xenografts of human pancreatic, kidney, lung, and breast cancers are downregulated by tetrac formulations. The integrin αvβ3 receptor site for thyroid hormone selectively regulates signal transduction pathways and distinguishes between unmodi- fied tetrac and the nanoparticulate formulation. The receptor also mediates nongenomic thyroid hormone effects on plasma membrane ion transporters and on intracellular protein trafficking.

Original languageEnglish
Pages (from-to)99-115
Number of pages17
JournalAnnual Review of Pharmacology and Toxicology
Volume51
DOIs
Publication statusPublished - Feb 10 2011
Externally publishedYes

Fingerprint

Thyroid Hormone Receptors
Membranes
Thyroid Hormones
Integrins
Cell membranes
Tumors
Cell Membrane
Thyronines
Signal transduction
Membrane Transport Proteins
Kidney Neoplasms
Cell proliferation
Cell Surface Receptors
Protein Transport
Pancreatic Neoplasms
Thyroxine
Heterografts
Blood Vessels
Signal Transduction
Lung Neoplasms

Keywords

  • angiogenesis
  • cancer cell proliferation
  • growth factors
  • integrin αvβ3
  • ion transport
  • nanoparticulate tetrac
  • protein trafficking
  • tetrac

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Membrane receptor for thyroid hormone : Physiologic and pharmacologic implications. / Davis, Paul J.; Davis, Faith B.; Mousa, Shaker A.; Luidens, Mary K.; Lin, Hung Yun.

In: Annual Review of Pharmacology and Toxicology, Vol. 51, 10.02.2011, p. 99-115.

Research output: Contribution to journalReview article

Davis, Paul J. ; Davis, Faith B. ; Mousa, Shaker A. ; Luidens, Mary K. ; Lin, Hung Yun. / Membrane receptor for thyroid hormone : Physiologic and pharmacologic implications. In: Annual Review of Pharmacology and Toxicology. 2011 ; Vol. 51. pp. 99-115.
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