PHYSIOLOGY OF THYROID HORMONE DEPENDENT GENE EXPRESSION

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DESCRIPTION (adapted from applicant's 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.