Expression Profiles of the Three Iodothyronine Deiodinases, D1, D2, and D3, in the Developing Rat1

Abstract

Thyroid hormone (TH) is essential for normal development in vertebrate species. Although the mechanisms by which TH regulates developmental processes are not fully understood, intracellular T3 levels are likely to be a critical aspect of the process. Furthermore, as different tissues and organs have specific temporal patterns of development, their T3 requirements may vary widely. Differential regulation of intracellular T3 levels in peripheral tissues as a result of differences in the activities of the three iodothyronine deiodinases (D1, D2, and D3) could offer an important means of achieving coordination of T3-dependent developmental processes among tissues. To obtain evidence for this concept we have documented the levels of expression of all three types of deiodinase in 11 tissues of the fetus, the neonate, and the adult rat. In most fetal tissues, D3 was the predominant deiodinase, but it declined after birth as the activities of D1 and D2 increased. Exceptions to this pattern were skin and brown adipose tissue (BAT), in which D2 activity was highest in the fetus, and testis and thyroid in which D2 activity was higher in the neonate than in the adult. D1 was the only 5'D enzyme expressed in liver, kidney and intestine at all stages studied, and D3 was not expressed in these tissues after birth. Thyroid, pituitary, and BAT expressed either D2 or D2 plus D1, but did not express D3 at any stage studied. Cerebrum, cerebellum, ovary, testis, skin, and placenta expressed all three deiodinases. Two other points were evident. First, the maximum 5'D activity attained, and thus presumably the amount of T3 generated, in liver, kidney, intestine, thyroid, pituitary, and BAT was very much higher than that in cerebrum, cerebellum, ovary, testis, skin, and placenta. Second, in the tissues where 5'D activity was relatively low, coexpression of D3 with D1 and D2 was the general rule, suggesting the need for very tight control of intracellular T3 levels. The findings are consistent with the view that the deiodinases play a major role in achieving the intracellular T3 levels that are optimal for the development of each tissue. Additional studies are in progress to demonstrate the functional consequences of these deiodinase expression patterns.