Nongenomic Actions of Thyroid Hormone Initiated at the Plasma Membrane or in Cytoplasm

Paul J. Davis, Faith B. Davis, Hung-Yun Lin, Aleck Hercbergs, Shaker A. Mousa

Research output: Contribution to journalReview article

Abstract

Genomic actions of thyroid hormone are initiated with intranuclear binding of the hormone by heterodimeric nuclear thyroid hormone receptor (TR) proteins that are transcription factors. There is increasing recent experimental appreciation of the existence of nongenomic actions of the hormone that are initiated in cytoplasm or at the plasma membrane. Those that begin in cytoplasm may involve nuclear TRs now recognized to reside in cytoplasm and may alter the state of the actin cytoskeleton or foster insertion into the plasma membrane of the Na,K-ATPase; cytoplasmic action
of the hormone via TR may also culminate downstream in the nucleus in the transcription of specific genes, such as hypoxia-inducible factor-1α. A plasma membrane receptor for L-thyroxine (T4) and 3, 5, 3’-triiodo-L-thyronine (T3) has been described on integrin αvβ3. Among the complex mitogen-activated protein kinase (MAPK; ERK1/2)-mediated activities initiated at the integrin receptor are tumor cell proliferation and angiogenesis. Shuttling of TRs between cytoplasm and nucleus may be promoted by thyroid hormone via the integrin. The hormonal actions attributable to integrin-liganded T4 or T3 can be reproduced by hormone analogues tethered to agarose or to nanoparticles that prevent cell entry of the hormone. Tetraiodothyoacetic acid (tetrac) is an inhibitor of the actions of T4 and T3 at the integrin. Tetrac has anti-proliferative and antiangiogenic activities that are currently under exploration.
Original languageEnglish
JournalHot Thyroidology
Publication statusPublished - 2009

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Thyroid Hormones
Integrins
Cytoplasm
Cell Membrane
Hormones
Thyroid Hormone Receptors
Thyronines
Hypoxia-Inducible Factor 1
Cytoplasmic and Nuclear Receptors
Mitogen-Activated Protein Kinases
Actin Cytoskeleton
Thyroxine
Nanoparticles
Sepharose
Transcription Factors
Cell Proliferation
Acids
Genes
Neoplasms
Proteins

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Nongenomic Actions of Thyroid Hormone Initiated at the Plasma Membrane or in Cytoplasm. / Davis, Paul J.; Davis, Faith B.; Lin, Hung-Yun; Hercbergs, Aleck; Mousa, Shaker A.

In: Hot Thyroidology, 2009.

Research output: Contribution to journalReview article

Davis, Paul J. ; Davis, Faith B. ; Lin, Hung-Yun ; Hercbergs, Aleck ; Mousa, Shaker A. / Nongenomic Actions of Thyroid Hormone Initiated at the Plasma Membrane or in Cytoplasm. In: Hot Thyroidology. 2009.
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abstract = "Genomic actions of thyroid hormone are initiated with intranuclear binding of the hormone by heterodimeric nuclear thyroid hormone receptor (TR) proteins that are transcription factors. There is increasing recent experimental appreciation of the existence of nongenomic actions of the hormone that are initiated in cytoplasm or at the plasma membrane. Those that begin in cytoplasm may involve nuclear TRs now recognized to reside in cytoplasm and may alter the state of the actin cytoskeleton or foster insertion into the plasma membrane of the Na,K-ATPase; cytoplasmic actionof the hormone via TR may also culminate downstream in the nucleus in the transcription of specific genes, such as hypoxia-inducible factor-1α. A plasma membrane receptor for L-thyroxine (T4) and 3, 5, 3’-triiodo-L-thyronine (T3) has been described on integrin αvβ3. Among the complex mitogen-activated protein kinase (MAPK; ERK1/2)-mediated activities initiated at the integrin receptor are tumor cell proliferation and angiogenesis. Shuttling of TRs between cytoplasm and nucleus may be promoted by thyroid hormone via the integrin. The hormonal actions attributable to integrin-liganded T4 or T3 can be reproduced by hormone analogues tethered to agarose or to nanoparticles that prevent cell entry of the hormone. Tetraiodothyoacetic acid (tetrac) is an inhibitor of the actions of T4 and T3 at the integrin. Tetrac has anti-proliferative and antiangiogenic activities that are currently under exploration.",
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AU - Lin, Hung-Yun

AU - Hercbergs, Aleck

AU - Mousa, Shaker A.

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N2 - Genomic actions of thyroid hormone are initiated with intranuclear binding of the hormone by heterodimeric nuclear thyroid hormone receptor (TR) proteins that are transcription factors. There is increasing recent experimental appreciation of the existence of nongenomic actions of the hormone that are initiated in cytoplasm or at the plasma membrane. Those that begin in cytoplasm may involve nuclear TRs now recognized to reside in cytoplasm and may alter the state of the actin cytoskeleton or foster insertion into the plasma membrane of the Na,K-ATPase; cytoplasmic actionof the hormone via TR may also culminate downstream in the nucleus in the transcription of specific genes, such as hypoxia-inducible factor-1α. A plasma membrane receptor for L-thyroxine (T4) and 3, 5, 3’-triiodo-L-thyronine (T3) has been described on integrin αvβ3. Among the complex mitogen-activated protein kinase (MAPK; ERK1/2)-mediated activities initiated at the integrin receptor are tumor cell proliferation and angiogenesis. Shuttling of TRs between cytoplasm and nucleus may be promoted by thyroid hormone via the integrin. The hormonal actions attributable to integrin-liganded T4 or T3 can be reproduced by hormone analogues tethered to agarose or to nanoparticles that prevent cell entry of the hormone. Tetraiodothyoacetic acid (tetrac) is an inhibitor of the actions of T4 and T3 at the integrin. Tetrac has anti-proliferative and antiangiogenic activities that are currently under exploration.

AB - Genomic actions of thyroid hormone are initiated with intranuclear binding of the hormone by heterodimeric nuclear thyroid hormone receptor (TR) proteins that are transcription factors. There is increasing recent experimental appreciation of the existence of nongenomic actions of the hormone that are initiated in cytoplasm or at the plasma membrane. Those that begin in cytoplasm may involve nuclear TRs now recognized to reside in cytoplasm and may alter the state of the actin cytoskeleton or foster insertion into the plasma membrane of the Na,K-ATPase; cytoplasmic actionof the hormone via TR may also culminate downstream in the nucleus in the transcription of specific genes, such as hypoxia-inducible factor-1α. A plasma membrane receptor for L-thyroxine (T4) and 3, 5, 3’-triiodo-L-thyronine (T3) has been described on integrin αvβ3. Among the complex mitogen-activated protein kinase (MAPK; ERK1/2)-mediated activities initiated at the integrin receptor are tumor cell proliferation and angiogenesis. Shuttling of TRs between cytoplasm and nucleus may be promoted by thyroid hormone via the integrin. The hormonal actions attributable to integrin-liganded T4 or T3 can be reproduced by hormone analogues tethered to agarose or to nanoparticles that prevent cell entry of the hormone. Tetraiodothyoacetic acid (tetrac) is an inhibitor of the actions of T4 and T3 at the integrin. Tetrac has anti-proliferative and antiangiogenic activities that are currently under exploration.

KW - integrin αvβ3

KW - actin

KW - tetraiodothyroacetic acid

KW - phosphatidylinositol 3-kinase

KW - mitogenactivated protein kinase

KW - nanoparticles

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M3 - Review article

JO - Hot Thyroidology

JF - Hot Thyroidology

ER -