Minireview: Defining the roles of the iodothyronine deiodinases: current concepts and challenges

Abstract

As is typical of other hormone systems, the actions of the thyroid hormones (TH) differ from tissue to tissue depending upon a number of variables. In addition to varying expression levels of TH receptors and transporters, differing patterns of TH metabolism provide a critical mechanism whereby TH action can be individualized in cells depending on the needs of the organism. The iodothyronine deiodinases constitute a family of selenoenzymes that selectively remove iodide from thyroxine and its derivatives, thus activating or inactivating these hormones. Three deiodinases have been identified, and much has been learned regarding the differing structures, catalytic activities, and expression patterns of these proteins. Because of their differing properties, the deiodinases appear to serve varying functions that are important in regulating metabolic processes, TH action during development, and feedback control of the thyroid axis. This review will briefly assess these functional roles and others proposed for the deiodinases and examine some of the current challenges in expanding our knowledge of these important components of the thyroid homeostatic system.

Figure 1

Reactions catalyzed by the iodothyronine deiodinases. T₄ is a relatively poor substrate for 5′-deiodination by the D1, whereas 5-deiodination by this enzyme most efficiently uses the sulfated derivatives (at the 4′-position) of T₄ and T₃ as substrates. 5D, 5-Deiodination; 5′D, 5′-deiodination.

Figure 2

Proposed roles for the deiodinases in the systemic response of the thyroid axis to illness or nutritional deprivation. Recent studies have called these concepts into question (see text).