Pretranslational Regulation of Type 2 Deiodinase

Type 2 deiodinase (D2) is a highly potent selenoenzyme that catalyzes the first step of thyroid hormone action and its expression is under close, multilevel control. D2 expression is tissue specific and can be regulated by transcriptional and posttranscriptional mechanisms. There is now compelling evidence that D2 is critically important in triiodothyronine (T3) homeostasis as well as in several biologic processes in which thyroid hormone is involved. A host of factors are known to influence dio2 mRNA including the transcription factors that regulate the dio2 gene in different cell types. In particular, cyclic adenosine monophosphate (cAMP) and two homeodomain- containing proteins are relevant for its defined and highly dynamic expression pattern. Single nucleotide polymorphisms of the dio2 gene and other pre-translational events such as alternative splicing can potentially modulate D2 expression and ultimately T(3) generation. Given the wealth of data accumulated over the past two decades, we have attempted in this review to provide a comprehensive update on the pretranslational regulation of D2.