Thyroid hormone deiodination in target tissues--a regulatory role for the trace element selenium?
The three isozymes catalyzing deiodination of thyroid hormones and iodothyronines derived thereof exert a major role in tissue- and development-specific expression of thyroid hormone action in target tissues by activating the prohormone T4 to thyromimetically active T3 or by inactivating the prohormone T4 or active T3 in non-target tissues at inappropriate time points. These three isozymes, in cooperation with the enzymes responsible for non-deiodinative degradation of iodothyronines, thus act as "guardians of the gate" to nuclear thyroid hormone receptors and other cellular target sites for thyroid hormone action. Strict and distinct hormonal, nutritional and nerval regulation of expression of the deiodinase isozymes warrants a closely coordinated control of thyroid hormone action, which directs growth, differentiation, and basal metabolic functions in the developing and the adult organism both in the periphery and in the central nervous system. The integrative action of this essential homeostatic and dynamic ancient hormone system in higher vertebrates is under the influence of two essential trace elements, iodine and selenium, which both are inadequately available for man and life stock in great parts of the world. As soon as, and only if, iodine supplementation is achieved, attempts to establish adequate selenium supply for thyroid hormone synthesis, activation, metabolism and action should be made, but not the other way around. In this review, the physiological, biochemical and pharmacological properties of the three deiodinase isozymes are discussed in detail, with special attention to the role of selenium in regulation of type I 5'-deiodinase expression. The contribution of each deiodinase izozyme to the activation and inactivation of thyroid hormones in specific tissues is reviewed.
Köhrle
J
J
Medizinische Poliklinik, Universität Würzburg, Germany.
D000818:Animals; D003409:Congenital Hypothyroidism / Q000209:etiology; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism; D007455:Iodine / Q000378:metabolism* / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism; D012643:Selenium / Q000502:physiology*; D013963:Thyroid Hormones / Q000378:metabolism*
D007527:Isoenzymes; D013963:Thyroid Hormones; D007455:Iodine; D007453:Iodide Peroxidase; D012643:Selenium