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Physiol. Rev. 81: 1097-1142, 2001;
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Physiological Reviews, Vol. 81, No. 3, July 2001, pp. 1097-1142
Copyright ©2001 by the American Physiological Society

Physiological and Molecular Basis of Thyroid Hormone Action

Paul M. Yen

Molecular Regulation and Neuroendocrinology Section, Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

Yen, Paul M. Physiological and Molecular Basis of Thyroid Hormone Action. Physiol. Rev. 81: 1097-1142, 2001.Thyroid hormones (THs) play critical roles in the differentiation, growth, metabolism, and physiological function of virtually all tissues. TH binds to receptors that are ligand-regulatable transcription factors belonging to the nuclear hormone receptor superfamily. Tremendous progress has been made recently in our understanding of the molecular mechanisms that underlie TH action. In this review, we present the major advances in our knowledge of the molecular mechanisms of TH action and their implications for TH action in specific tissues, resistance to thyroid hormone syndrome, and genetically engineered mouse models.




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A. J Klecha, A. M Genaro, G. Gorelik, M. L. Barreiro Arcos, D. M. Silberman, M. Schuman, S. I Garcia, C. Pirola, and G. A Cremaschi
Integrative study of hypothalamus-pituitary-thyroid-immune system interaction: thyroid hormone-mediated modulation of lymphocyte activity through the protein kinase C signaling pathway.
J. Endocrinol., April 1, 2006; 189(1): 45 - 55.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
P. M. Yen
Thyroid hormones and 3,5-diiodothyropropionic Acid: new keys for new locks.
Endocrinology, April 1, 2006; 147(4): 1598 - 1601.
[Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
N. M. Storey, S. Gentile, H. Ullah, A. Russo, M. Muessel, C. Erxleben, and D. L. Armstrong
Rapid signaling at the plasma membrane by a nuclear receptor for thyroid hormone
PNAS, March 28, 2006; 103(13): 5197 - 5201.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
Y. Liu, X. Xia, J. D. Fondell, and P. M. Yen
Thyroid Hormone-Regulated Target Genes Have Distinct Patterns of Coactivator Recruitment and Histone Acetylation
Mol. Endocrinol., March 1, 2006; 20(3): 483 - 490.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
T. Iwasaki, A. Takeshita, W. Miyazaki, W. W. Chin, and N. Koibuchi
The Interaction of TR{beta}1-N Terminus with Steroid Receptor Coactivator-1 (SRC-1) Serves a Full Transcriptional Activation Function of SRC-1
Endocrinology, March 1, 2006; 147(3): 1452 - 1457.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
L. A. Arnold, E. Estebanez-Perpina, M. Togashi, N. Jouravel, A. Shelat, A. C. McReynolds, E. Mar, P. Nguyen, J. D. Baxter, R. J. Fletterick, et al.
Discovery of Small Molecule Inhibitors of the Interaction of the Thyroid Hormone Receptor with Transcriptional Coregulators
J. Biol. Chem., December 30, 2005; 280(52): 43048 - 43055.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
D. R. Buchholz, B. D. Paul, and Y.-B. Shi
Gene-specific Changes in Promoter Occupancy by Thyroid Hormone Receptor during Frog Metamorphosis: IMPLICATIONS FOR DEVELOPMENTAL GENE REGULATION
J. Biol. Chem., December 16, 2005; 280(50): 41222 - 41228.
[Abstract] [Full Text] [PDF]

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 J. Exp. Biol.Home page
A. Heyland and L. L. Moroz
Cross-kingdom hormonal signaling: an insight from thyroid hormone functions in marine larvae
J. Exp. Biol., December 1, 2005; 208(23): 4355 - 4361.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
L. C. Moeller, A. M. Dumitrescu, and S. Refetoff
Cytosolic Action of Thyroid Hormone Leads to Induction of Hypoxia-Inducible Factor-1{alpha} and Glycolytic Genes
Mol. Endocrinol., December 1, 2005; 19(12): 2955 - 2963.
[Abstract] [Full Text] [PDF]

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 Eur J EndocrinolHome page
A. L. D. Riis, T. K. Hansen, S. Thiel, C. H. Gravholt, S. Gjedde, L. C. Gormsen, J. O. L. Jorgensen, J. Weeke, and N. Moller
Thyroid hormone increases mannan-binding lectin levels
Eur. J. Endocrinol., November 1, 2005; 153(5): 643 - 649.
[Abstract] [Full Text] [PDF]

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 J EndocrinolHome page
K Boelaert and J A Franklyn
Thyroid hormone in health and disease
J. Endocrinol., October 1, 2005; 187(1): 1 - 15.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
H. Ying, F. Furuya, M. C. Willingham, J. Xu, B. W. O'Malley, and S.-y. Cheng
Dual Functions of the Steroid Hormone Receptor Coactivator 3 in Modulating Resistance to Thyroid Hormone
Mol. Cell. Biol., September 1, 2005; 25(17): 7687 - 7695.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
S. Demolombe, C. Marionneau, S. Le Bouter, F. Charpentier, and D. Escande
Functional genomics of cardiac ion channel genes
Cardiovasc Res, August 15, 2005; 67(3): 438 - 447.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
M.-B. Poirier, G. Hamann, M.-E. Domingue, M. Roy, T. Bardati, and M.-F. Langlois
General Receptor for Phosphoinositides 1, a Novel Repressor of Thyroid Hormone Receptor Action that Prevents Deoxyribonucleic Acid Binding
Mol. Endocrinol., August 1, 2005; 19(8): 1991 - 2005.
[Abstract] [Full Text] [PDF]

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X. Prieur, T. Huby, H. Coste, F. G. Schaap, M. J. Chapman, and J. C. Rodriguez
Thyroid Hormone Regulates the Hypotriglyceridemic Gene APOA5
J. Biol. Chem., July 29, 2005; 280(30): 27533 - 27543.
[Abstract] [Full Text] [PDF]

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B. D. Paul, D. R. Buchholz, L. Fu, and Y.-B. Shi
Tissue- and Gene-specific Recruitment of Steroid Receptor Coactivator-3 by Thyroid Hormone Receptor during Development
J. Biol. Chem., July 22, 2005; 280(29): 27165 - 27172.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
L. Johansson, M. Rudling, T. S. Scanlan, T. Lundasen, P. Webb, J. Baxter, B. Angelin, and P. Parini
Selective thyroid receptor modulation by GC-1 reduces serum lipids and stimulates steps of reverse cholesterol transport in euthyroid mice
PNAS, July 19, 2005; 102(29): 10297 - 10302.
[Abstract] [Full Text] [PDF]

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S. Y Chan, M. H Andrews, R. Lingas, C. J McCabe, J. A Franklyn, M. D Kilby, and S. G Matthews
Maternal nutrient deprivation induces sex-specific changes in thyroid hormone receptor and deiodinase expression in the fetal guinea pig brain
J. Physiol., July 15, 2005; 566(2): 467 - 480.
[Abstract] [Full Text] [PDF]

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M. Togashi, P. Nguyen, R. Fletterick, J. D. Baxter, and P. Webb
Rearrangements in Thyroid Hormone Receptor Charge Clusters That Stabilize Bound 3,5',5-Triiodo-L-thyronine and Inhibit Homodimer Formation
J. Biol. Chem., July 8, 2005; 280(27): 25665 - 25673.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
B. D. Paul, L. Fu, D. R. Buchholz, and Y.-B. Shi
Coactivator Recruitment Is Essential for Liganded Thyroid Hormone Receptor To Initiate Amphibian Metamorphosis
Mol. Cell. Biol., July 1, 2005; 25(13): 5712 - 5724.
[Abstract] [Full Text] [PDF]

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 Hum Mol GenetHome page
D. French, M. R. Wilkinson, W. Yang, L. de Chaisemartin, E. H. Cook, S. Das, M. J. Ratain, W. E. Evans, J. R. Downing, C.-H. Pui, et al.
Global gene expression as a function of germline genetic variation
Hum. Mol. Genet., June 15, 2005; 14(12): 1621 - 1629.
[Abstract] [Full Text] [PDF]

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 J Mol EndocrinolHome page
C Feart, J Vallortigara, D Higueret, B Gatta, A Tabarin, V Enderlin, P Higueret, and V Pallet
Decreased expression of retinoid nuclear receptor (RAR{alpha} and RAR{gamma}) mRNA determined by real-time quantitative RT-PCR in peripheral blood mononuclear cells of hypothyroid patients
J. Mol. Endocrinol., June 1, 2005; 34(3): 849 - 858.
[Abstract] [Full Text] [PDF]

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 J EndocrinolHome page
G M Ledda-Columbano, A Perra, M Pibiri, F Molotzu, and A Columbano
Induction of pancreatic acinar cell proliferation by thyroid hormone
J. Endocrinol., June 1, 2005; 185(3): 393 - 399.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
X. Meng, P. Webb, Y.-F. Yang, M. Shuen, A. F. Yousef, J. D. Baxter, J. S. Mymryk, and P. G. Walfish
E1A and a nuclear receptor corepressor splice variant (N-CoRI) are thyroid hormone receptor coactivators that bind in the corepressor mode
PNAS, May 3, 2005; 102(18): 6267 - 6272.
[Abstract] [Full Text] [PDF]

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 J EndocrinolHome page
R M McAllister, I Albarracin, E M Price, T K Smith, J R Turk, and K D Wyatt
Thyroid status and nitric oxide in rat arterial vessels
J. Endocrinol., April 1, 2005; 185(1): 111 - 119.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
Y. Liu, S. Ando, X. Xia, R. Yao, M. Kim, J. Fondell, and P. M. Yen
p62, A TFIIH Subunit, Directly Interacts with Thyroid Hormone Receptor and Enhances T3-Mediated Transcription
Mol. Endocrinol., April 1, 2005; 19(4): 879 - 884.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
T. Morimura, K. Tsunekawa, T. Kasahara, K. Seki, T. Ogiwara, M. Mori, and M. Murakami
Expression of Type 2 Iodothyronine Deiodinase in Human Osteoblast Is Stimulated by Thyrotropin
Endocrinology, April 1, 2005; 146(4): 2077 - 2084.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. L. Goodson, B. A. Jonas, and M. L. Privalsky
Alternative mRNA Splicing of SMRT Creates Functional Diversity by Generating Corepressor Isoforms with Different Affinities for Different Nuclear Receptors
J. Biol. Chem., March 4, 2005; 280(9): 7493 - 7503.
[Abstract] [Full Text] [PDF]

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 Eur J EndocrinolHome page
C Feart, V Pallet, C Boucheron, D Higueret, S Alfos, L Letenneur, J F Dartigues, and P Higueret
Aging affects the retinoic acid and the triiodothyronine nuclear receptor mRNA expression in human peripheral blood mononuclear cells
Eur. J. Endocrinol., March 1, 2005; 152(3): 449 - 458.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
C. Angelin-Duclos, C. Domenget, A. Kolbus, H. Beug, P. Jurdic, and J. Samarut
Thyroid hormone T3 acting through the thyroid hormone {alpha} receptor is necessary for implementation of erythropoiesis in the neonatal spleen environment in the mouse
Development, March 1, 2005; 132(5): 925 - 934.
[Abstract] [Full Text] [PDF]

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 J Mol EndocrinolHome page
L. Schneider, C. El-Yazidi, A. Dace, M. Maraninchi, R. Planells, A. Margotat, and J. Torresani
Expression of the 1,25-(OH)2 vitamin D3 receptor gene during the differentiation of mouse Ob17 preadipocytes and cross talk with the thyroid hormone receptor signalling pathway
J. Mol. Endocrinol., February 1, 2005; 34(1): 221 - 235.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
P. M. Yen
Studying Hormonal Regulation by Microarrays: Distinguishing the Trees from the Forest
J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1241 - 1242.
[Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
L. C. Moeller, A. M. Dumitrescu, R. L. Walker, P. S. Meltzer, and S. Refetoff
Thyroid Hormone Responsive Genes in Cultured Human Fibroblasts
J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 936 - 943.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
B. J. Mengeling, F. Pan, and M. L. Privalsky
Novel Mode of Deoxyribonucleic Acid Recognition by Thyroid Hormone Receptors: Thyroid Hormone Receptor {beta}-Isoforms Can Bind as Trimers to Natural Response Elements Comprised of Reiterated Half-Sites
Mol. Endocrinol., January 1, 2005; 19(1): 35 - 51.
[Abstract] [Full Text] [PDF]


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