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      Metabolism of the Thyroid Hormones

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          This review covers the current knowledge about the various metabolic pathways involved in the conversion of thyroid hormones to the thyromimetically active and inactive iodothyronines. The concerted mechanism of systemic and local production of iodothyronines by tissue-specific iodothyronine deiodinase isozymes will ultimately determine the expression of thyroid hormone action. This is exemplified for the regulation of synthesis and release of TSH by iodothyronines at the pituitary level. Iodothyronine metabolites, e.g. Triac, rT<sub>3</sub> and T<sub>3</sub> amine may modulate TSH secretion, and alterations of local pituitary deiodination (e.g. iopanoate inhibition) influence diurnal TSH secretion without changing TRH-dependent episodic TSH secretion pattern. A summary of structure-activity relationships of > 200 naturally occurring and synthetic ligands of rat liver type I iodothyronine deiodinase isozyme propylthiouracil-sensitive) in vitro allows the design of iodothyronine analogues which either serve as specific substrates or antagonists of iodothyronine binding and metabolizing proteins. Furthermore, a complete picture of the ligand-complementary active site of the type I isozyme can be derived. A synthetic ‘structurally optimized’ iodothyronine-analogue flavonoid inhibitor of the type I deiodinase is able to displace T<sub>4</sub> from binding to thyroxine-binding prealbumin and leads to unexpected organ-specific alterations of thyroid hormone metabolism and expression of thyroid hormone actions in an animal model. Therefore, for a complete understanding of thyroid hormone metabolism and action, thyroid hormone transport, cellular compartmentalization, and alternate pathways also have to be considered.

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          Author and article information

          Horm Res Paediatr
          Hormone Research in Paediatrics
          S. Karger AG
          28 November 2008
          : 26
          : 1-4
          : 58-78
          Medizinische Hochschule Hannover, Abteilung für klinische Endokrinologie, Departement Innere Medizin, Hannover, FRG
          180686 Horm Res 1987;26:58–78
          © 1987 S. Karger AG, Basel

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          Pages: 21
          Full Invited Paper


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