The Deiodinases: their Identification and Cloning of their Genes.

In this minireview we provide an historical outline of the events that led to the identification and characterization of the deiodinases, the recognition that deiodination plays a major role in thyroid hormone action, and the cloning of the three deiodinase genes. The story starts in 1820 when it was first determined that elemental iodine was important for normal thyroid function. Almost a hundred years later it was found that the primary active principle of the gland, thyroxine (T4), contains iodine. Once radioactive iodine became available in the 1940s it was demonstrated that the metabolism of the T4 included deiodination, but at the time it was assumed to be merely a degradative process. However, this view was questioned after the discovery of 3,5,3'-triiodothyronine in 1952. We then discuss in some detail the events of the next twenty years, that included some failures followed by the successful demonstration that deiodination is indeed essential to normal thyroid hormone action. Finally, we describe how the three deiodinases were identified and characterized and their genes cloned.