In VivoInhibition of the 5′-Deiodinase Type II in Brain Cortex and Pituitary by Reverse Triiodothyronine*

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Abstract
To study the effect of rT3 on the 5''-deiodinase type II (5''D-II) of rat brain cortex and anterior pituitary, daily infusions of rT3 at rates of 0.5, 1.5, 4.5, and 13.5 nmol/day. .cntdot.100 g body weight were given to a total of 87 hypothyroid rats. rT3 inhibited the 5''D-II activity in the total homogenate and in the microsomal fraction in the brain cortex, inhibition becoming significant (28-33%) with the infusion of 4.5 nmol/day .cntdot.100 g body weight, at serum levels of 2.4 pmol rT3/ml. Infusion of 13.5 nmol/day .cntdot. 100 g body weight produced 71-73% inhibition. In homogenates of the anterior pituitary, inhibition was significant with infusions of 13.5 nmol/day .cntdot. 100 g body weight (30%). To examine how rT3 might inhibit 5''D-II activity, labeled rT3 (137 .mu.Ci/day) was infused into 4 hypothyroid rats, and the rT3 content in the homogenate and in the cell subfractions was measured by HPLC. No rT3 was detectable in the nuclei, and less than 1% was found in the microsomal fraction. The infused rT3 was thus no longer present in the microsome preparations and homogenates. The inhibitory effect of rT3 was also compared with that of T4. Serum T4 levels of 45 pmol/ml were required in order to inhibit 5''D-II to the same extent as with 7 pmol rT3/ml. The requirement of this high serum level of T4 excludes the potential role of T4 impurities in the infused rT3 preparation. We therefore conclude that rT3 inhibits 5''D-II in brain cortex per se independently of T4.