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.

Changes in acetylcholinesterase, Na+,K+-ATPase, and Mg2+-ATPase activities in the frontal cortex and the hippocampus of hyper- and hypothyroid adult rats

“…Furthermore, a different expression of deiodinases in the various brain regions [55], along with the functional heterogeneity of the CNS neurotransmission complex, may be a reflection of the lack of uniformity in the profile of the examined enzyme activities [43,[56][57][58][59]. In addition, in another field of our investigation involving the THs, we concluded that hyperand hypothyroidism seem to be 2 examples of states that cannot be considered as opposing in terms of the response of the (hyper-or hypothyroid) heart to ischemic stress, but are 2 different states that induce distinct forms of adaptation to ischemia (possibly through different mechanisms) [32,60,61].…”

Thyroid Hormones affect the Level and Activity of Nitric Oxide Synthase in Rat Cerebral Cortex during Postnatal Development

“…Although these parameters indicated clearly that marked systemic hyper-and hypothyroidism developed, the T3 level of the cerebral cortex changed only moderately in the treated animals compared to control. In the latter phenomenon the regulatory role of brain deiodinases (among them presumably type D2) could be implicated, since this enzyme converts T4 to the potent form of T3 [16,17]. Finely tuned D2 activity can protect the CNS from significant changes of systemic TH level and results in a steady state TH level in the brain for a prolonged period, even up to 20 days [18,19].…”

Is there a role for thyroid hormone on spermatogenesis?

“…This suggests that D2 and D3 might be expressed in different testicular cell types localized in specific regions of the organ, as seems to be the case in brain (Courtin et al, 2005). Indeed, very little is known about D2 and D3 specific cellular localization in the developing and mature testis and the level at which they are regulated by thyroid status in these different stages.…”