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.

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