Effects of Congenital Hypothyroidism and Partial and Complete Food Deprivation on Phenolic and Tyrosyl Ring Iodothyronine Deiodination in Rat Brain*

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Abstract
We have investigated the effects of congenital hypothyroidism, partial nutritional deficiency in the neonatal period, and total food deprivation in adulthood on thyroid hormone deiodinative metabolism in rat brain tissue. Congenital hypothyroidism was induced by adding 0.02% methimazole to the drinking water of pregnant rats from gestational day 17 through the end of lactation. T4 5′-deiodination rates were 4-fold higher in cerebral cortical homogenates of the hypothyroid pups than in homogenates of normal cortex at 1 day and remained higher at 7, 14, and 21 days. In cerebellar and hypothalamic homogenates, T4 5′-deiodination rates were unmeasurably low at 1 day in hypothyroid and control groups, but at 7, 14, and 21 days, rates were 4-5 times higher in tissue from the hypothyroid rats. In incubations with 2 μM T3, T3 tyrosyl ring deiodination was measurable only in hypothalamic homogenates, in which there was no difference between the groups at 1, 7, 14, or 21 days. Neonatal rats were rendered undernourished by limiting lactating mothers to half the normal chow intake from birth to 7 days. The food-limited pups had subnormal weights, subnormal mean serum TSH concentrations, mean serum T4 concentrations elevated to nearly twice normal, and, probably, elevated serum free T4 concentrations. The undernourished pups demonstrated decreased T4 5′-deiodination to 79% of control in cerebral cortical homogenates, with no change in T3 tyrosyl deiodination, measured at approximately 0.2 nM T3, in cerebral cortical or hypothalamic homogenates. Adult rats, subjected to fasting for 72 h, had significantly lower mean serum T4 and TSH concentrations than fed controls and significantly higher T4 5′-deiodination rates in hypothalamic homogenates (162% of control), with no significant change in T4 5′-deiodination in cerebral cortical homogenates and no change in T3 tyrosyl deiodination in cerebral cortical or hypothalamic homogenates. These results show that thyroid status is an important regulator of T4 5′-deiodinase activity in the immature rat brain, as it is in the adult rat brain. In contrast, hypothyroidism appears not to affect the brain tyrosyl ring deiodinase through 21 days of age, although activity of this enzyme has been found to be subnormal in the hypothyroid adult brain. Changes in the thyroid hormone economy of the rat in partial food deprivation differ greatly from the changes seen in total fasting. Reciprocal changes of T4 5′-deiodinase activity and serum thyroid hormones suggest that the increases or decreases in serum hormone concentrations induced by dietary manipulation might result in intracellular hyper-or hypothyroidism in certain brain regions.