Abstract

The focus of this proposal is to examine the critical components in TH action which might result in tissue specificity. The structural and biochemical explanations for the functional differences between the alpha 1 and beta 1 receptors using chimeric alpha 1-beta 1 and mutated receptors both alone and during interactions with other ligand-dependent and tissue specific nuclear proteins will be determined. The critical half-site sequences and motif arrangements of TREs from the rat alpha myosin heavy chain and malic enzyme genes will be compared to those defined in the rat growth hormone gene.The biochemical interactions of the two receptors and functionally informative mutants with all three TREs will be analyzed. Transient transfection systems will be used to vary the quantity, type, and ratio of normal and mutant receptors as well as TREs upstream of the reporter genes. Cells will be exposed to THs to examine the biological significance of the tissue specific, differential TH receptor (THR) saturation present in euthyroid rats.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK044128-03
Application #
2143530
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1992-01-15
Project End
1996-12-31
Budget Start
1994-02-20
Budget End
1994-12-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Wassner, Ari J; Jugo, Rebecca H; Dorfman, David M et al. (2017) Myocardial Induction of Type 3 Deiodinase in Dilated Cardiomyopathy. Thyroid 27:732-737
Luongo, Cristina; Martin, Cecilia; Vella, Kristen et al. (2015) The selective loss of the type 2 iodothyronine deiodinase in mouse thyrotrophs increases basal TSH but blunts the thyrotropin response to hypothyroidism. Endocrinology 156:745-54
Wittmann, Gábor; Harney, John W; Singru, Praful S et al. (2014) Inflammation-inducible type 2 deiodinase expression in the leptomeninges, choroid plexus, and at brain blood vessels in male rodents. Endocrinology 155:2009-19
Maynard, Michelle A; Marino-Enriquez, Adrian; Fletcher, Jonathan A et al. (2014) Thyroid hormone inactivation in gastrointestinal stromal tumors. N Engl J Med 370:1327-34
Salvatore, Domenico; Simonides, Warner S; Dentice, Monica et al. (2014) Thyroid hormones and skeletal muscle--new insights and potential implications. Nat Rev Endocrinol 10:206-14
Dentice, Monica; Ambrosio, Raffaele; Damiano, Valentina et al. (2014) Intracellular inactivation of thyroid hormone is a survival mechanism for muscle stem cell proliferation and lineage progression. Cell Metab 20:1038-48
Zavacki, Ann Marie; Larsen, P Reed (2013) RTH?, a newly recognized phenotype of the resistance to thyroid hormone (RTH) syndrome in patients with THRA gene mutations. J Clin Endocrinol Metab 98:2684-6
Hong, Eun-Gyoung; Kim, Brian W; Jung, Dae Young et al. (2013) Cardiac expression of human type 2 iodothyronine deiodinase increases glucose metabolism and protects against doxorubicin-induced cardiac dysfunction in male mice. Endocrinology 154:3937-46
Dentice, Monica; Marsili, Alessandro; Zavacki, Annmarie et al. (2013) The deiodinases and the control of intracellular thyroid hormone signaling during cellular differentiation. Biochim Biophys Acta 1830:3937-45
Larsen, P Reed; Zavacki, Ann Marie (2012) The role of the iodothyronine deiodinases in the physiology and pathophysiology of thyroid hormone action. Eur Thyroid J 1:232-242

Showing the most recent 10 out of 54 publications