The roles of the iodothyronine deiodinases in mammalian development

The thyroid hormones (TH) are essential for normal development in vertebrate species. This review considers the roles that the three deiodinases, types 1, 2 and 3 (D1, D2, and D3), play in regulating intracellular levels of TH during this critical period. The focus is on rodents and humans with emphasis on brain development. There is little evidence to suggest that the D1 plays a significant role in development and this is substantiated by the absence of any obvious developmental impairment in a D1-deficient mouse model. There is, however, compelling indirect evidence pertaining to the importance of the D2 in development, particularly with respect to that of the brain. However, surprisingly, a D2-deficient mouse model exhibits a very mild phenotype. This, together with the fact that D2 activity is increased in hypothyroidism, suggests that this deiodinase may be of greater importance in development when supplies of thyroxine are limited. The D3 is clearly essential for development in the euthyroid mammal. Information, both indirect and that obtained from a D3-deficent mouse model, strongly suggests that its presence in placenta, uterus and some fetal tissues are critical for limiting exposure of fetal tissues to inappropriate levels of TH.