Acute Posttranscriptional Regulation of Cerebrocortical and Pituitary Iodothyronine 5′-Deiodinases by Thyroid Hormone*

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Abstract
Cerebrocortical and pituitary iodothyronine 5''-deiodinases produce 50% or more of the T3 [triiodothyronine] found in these tissues and show rapid 3- to 5-fold changes in response to changes in the thyroid status. Since many T3 responses are initiated in the cell nucleus and require protein synthesis, the influence of cycloheximide and actinomycin D on the acute T3 suppression of cerebrocortical and pituitary 5''-deiodinase activities in hypothyroid rats was studied. Cycloheximide inhibited protein synthesis by > 95%, but did not prevent the rapid (4 h) T3-mediated decreases in 5''-deiodinase activity. In the presence of cycloheximide, T3 decreased enzyme activity by > 85%, with a t1/2 of .apprx. 70 min in the cerebral cortex and .apprx. 110 min in the pituitary. In vitro, neither T3 nor cycloheximide in large excess had any effect on enzyme activity. In cycloheximide-treated rats, cerebrocortical 5''-deiodinase activity decreased with a fractional turnover rate (k) of 1.2 h-1 in euthyroid and 0.07 h-1 in hypothyroid rats, respectively, with corresponding steady state enzyme levels of 18 .+-. 3 and 145 .+-. 9 U/mg protein. The resulting production rates of cerebrocortical 5''-deiodinase were 22 and 10 U/mg protein .cntdot. h. Actinomycin D failed to alter either the cerebrocortical 5''-deiodinase in euthyroid rats in 4 h or the inhibitory effect of T3, but inhibited RNA synthesis by > 70%. The T3-dependent fall in cerebrocortical 5''-deiodinase is mediated by a posttranscriptional mechanism that ultimately increases the rate of degradation/inactivation of the enzyme.

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