Anatomical Distribution of Phenolic and Tyrosyl Ring Iodothyronine Deiodinases in the Nervous System of Normal and Hypothyroid Rats*

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Abstract
We have evaluated regional differences in T4 5′-deiodinase and iodothyronine tyrosyl ring deiodinase activities and assessed the effect of hypothyroidism on these activities in the rat nervous system. T4 5′-deiodination and T3 tyrosyl ring deiodination were both measured by radiometric assays at 37 C in the presence of 100 mM dithiothreitol in homogenates of cerebral cortex, corpus striatum, midbrain, hypothalamus, cerebellum, brain stem, spinal cord, brachial plexus, and sciatic nerve from normal and hypothyroid rats. T4 5′-deiodinase activity was present throughout the central nervous system. In both groups, the highest mean reaction rates were in cerebral cortical and cerebellar homogenates. The lowest mean rate in normal rats was in spinal cord homogenates, and the lowest mean rate in the hypothyroid rats was in hypothalamic homogenates, with spinal cord being the next lowest. In each central nervous system region, T4 5′-deiodination rates were significantly higher in hypothyroid tissue than in normal tissue. No T4 5′-deiodination was detected in homogenates of brachial plexus or sciatic nerve. Iodothyronine tyrosyl ring deiodinase activity was also distributed widely throughout the central nervous system. In both groups of rats, conversion of T3 to 3,3′-diiodothyronine and 3′- iodothyronine was much more rapid in homogenates of cerebral cortex, corpus striatum, midbrain, and hypothalamus, which originate rostral to the rhombencephalon than in homogenates of cerebellum, brainstem, and spinal cord, which originate lower on the neuraxis. For all central nervous system regions except the spinal cord, T3 tyrosyl ring deiodination rates were significantly higher in homogenates of normal tissue than in homogenates of hypothyroid tissue. T3 tyrosyl ring deiodination was not detectable in brachial plexus or sciatic nerve homogenates. These results show that hypothyroidism modulates the activity of both deiodinase enzymes throughout the central nervous system, superimposing an increase in T4 5′-deiodinase activity and a decrease in iodothyronine tyrosyl ring deiodinase activity upon the underlying anatomical patterns. Thus, the entire central nervous system responds to altered thyroid status at the molecular level, as it does at the functional level.