Thyroid Hormone Metabolism: A Historical Perspective.

In this article, starting with the recognition that iodine is essential for normal thyroid function and is a component of thyroid hormone (TH) molecules, we discuss the many seminal observations and discoveries that have led to identification of various pathways of TH metabolism and their potential roles in TH economy and action. We then recount evidence that TH metabolism participates in maintaining the appropriate content of active hormone in a TH-responsive tissue or cell. Thus, metabolism of the TH is not merely a means by which it is degraded and eliminated from the body, but an essential component of an intricate system by which the thyroid exerts its multiple regulatory effects on almost all organs and tissues.

The Deiodinases: Their Identification and Cloning of Their Genes.

In this minireview, we provide a 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 3 deiodinase genes. The story starts in 1820, when it was first determined that elemental iodine was important for normal thyroid function. Almost 100 years later, it was found that the primary active principle of the gland, T4, contains iodine.

The Intrinsic Activity of Thyroxine Is Critical for Survival and Growth and Regulates Gene Expression in Neonatal Liver.

Thyroxine (T4) is generally considered to be a prohormone that requires conversion to triiodothyronine (T3) to exert biological activity. Although evidence suggests that T4 has intrinsic activity, it is questionable if this activity has any physiological relevance. To answer this question, triple knockout (KO) mice (Triples) that cannot express the types 1 (D1) and 2 (D2) deiodinase and the genes were generated.

triiodothyronine formation from thyrocytes activated by thyroid-stimulating hormone.

The thyroid gland secretes primarily tetraiodothyronine (T), and some triiodothyronine (T). Under normal physiological circumstances, only one-fifth of circulating T is directly released by the thyroid, but in states of hyperactivation of thyroid-stimulating hormone receptors (TSHRs), patients develop a syndrome of relative T toxicosis. Thyroidal T production results from iodination of thyroglobulin (TG) at residues Tyr and Tyr, whereas thyroidal T production may originate in several different ways.