Mechanism of Thyroid Hormone Action
The pathway through which thyroid hormone controls metabolism begins with secretion of thyroxine and triiodothyronine by the thyroid, peripheral deiodination of about 1/3 of secreted T4 to T3, and uptake of the iodothyronines by passive and active mechanisms into the cell. Thyroid hormone in serum and in cell cytosol exists largely bound to proteins in a reversible equilibrium, with a tiny free fraction. It is this free fraction which equilibrates between serum and cells. Free hormone in the cell cytoplasm, and T3 generated from T4 within the cell diffuse into the nucleus and bind to thyroid hormone receptor proteins. These receptors may exist in the nucleoplasm, or, more likely, largely attached to DNA. Occupancy of receptors which are bound to specific sequences in DNA (thyroid response elements or TREs) leads to activation or repression of transcription, altered amounts of mRNA, and thus altered protein synthesis. It is the final alteration in amounts of specific proteins--enzymes, structural proteins, DNA binding proteins, which carry out the “physiologic” functions which we recognize as the increased metabolic activity seen as an individual moves from hypothyroidism to thyrotoxicosis. The key elements in this response are the thyroid hormone itself, the nuclear receptor proteins (TRs), and the TREs on hormone responsive genes.
KeywordsThyroid Hormone Thyroid Hormone Receptor Thyroid Hormone Action Euthyroid Sick Syndrome Bind Thyroid Hormone
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