Cerebral Hypothyroidism in Rats with Adult-Onset Iodine Deficiency*

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Abstract
Rats fed chronically a low I diet may have low serum thyroxine [T4] and high circulating TSH, despite normal serum triiodothyronine [T3]. As the brain depends to a great extent on intracellular generation of T3 from T4 for its total and nuclear T3, 2 experiments were carried out to determine whether the brain of I-deficient rats may become hypothyroid, despite normal serum T3 levels. In both experiments previous data was confirmed showing that the pituitary and liver of I-deficient rats with very low plasma T4 levels are hypothyroid as compared to those of animals receiving the same diet supplemented with KI, though not as markedly as animals which had undetectable circulating levels of both T4 and T3 as a consequence of chronic ingestion of KClO4-, or of surgical thyroidectomy. The nuclear T3 content was decreased in the brain of iodine-deficent rats, as compared with the animals on the I-supplemented diet. The nuclear to plasma ratios of labeled T3 showed that the uptake of this hormone into liver and brain nuclei is not decreased in the I-deficient rats as compared with those on the I-supplemented diet. The decreased liver and brain nuclear T3 contents of I-deficient rats are likely to be a consequence of the marked reduction of their T4 pool, leading to decreased amounts of intracellularly generated T3. The number of spines on shafts of pyramidal neurons from the visual cortex of I-deficient rats was lower than that of rats fed the same diet supplemented with KI. Their distributions along the shaft were also not the same. Such changes might well be an index of cerebral hypothyroidism, as they are similar to those found after thyroidectomy of adult rats. Normal circulating T3 levels may not be sufficient to maintain brain euthyroidism in rats fed a diet I-deficient enough to result in very low ciruclating T4 levels.