Thyroid hormone deiodinases in the central and peripheral nervous system

Abstract

Thyroid hormones play a critical role in development and functioning of the nervous system. Deiodinases (type 2 [D2] and type 3 [D3]) contribute to the control of thyroid hormone action in the nervous system by regulating the local concentrations of triiodothyronine (T(3)), the main active thyroid hormone. Most brain T(3) is indeed locally formed by deiodination of thyroxine (T(4)). This reaction is catalyzed by D2 expressed in astrocytes throughout the brain and in tanycytes in the mediobasal hypothalamus. D3, which inactivates both T(4) and T(3), is mainly expressed in neurons also throughout the brain, with high expression in hippocampus and pyriform cortex. The regulation of deiodinases by many factors in addition to the thyroid hormones indicate that their role is not limited to mitigate the fluctuations in plasma T(4) and T(3). In contrast to the brain, deiodinases are not expressed in the adult peripheral nerve. Nerve lesions induce D2 in peripheral nerve sheaths and D3 in the endoneurial compartment containing Schwann cells. On the basis of available data summarized in this review, D2 and D3 clearly contribute to determine T(3) concentrations depending on the area of the nervous system, the state of development, and the pathophysiologic conditions.