Increases in Brain Nuclear Triiodothyronine Receptors Associated with Increased Triiodothyronine in Hyperthyroid and Hypothyroid Rats

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Abstract
Hormonal modulation of brain nuclear T3 receptors was examined in hyperthyroid rats given 40 μg T3/100 g BW for 3 days and in hypothyroid animals after thyroidectomy. The maximal binding capacity (Cmax) and equilibrium association constant (Ka) of the nuclear receptors were determined by Scatchard analysis with and without correction for endogenous T3 bound to the nuclear extract. After the administration of T3, the serum T3 level increased from 71.7 ± 13.5 (mean ± SD) to 525.6 ± 69.5 ng/100 ml (P < 0.001), and the T3 concentration in the brain nuclear extract increased from 0.113 ±0.052 to 0.314 ± 0.062 ng/mg DNA (P < 0.001). Hepatic mitochondrial aglycerophosphate dehydrogenase activity increased significantly (P < 0.001), but the hepatic DNA content was unchanged. The Cmax of the brain nuclear receptor increased from 183.7 ± 93.6 to 321.1 ± 60.9 pg T3/mg DNA (P < 0.05), but the Ka was unchanged when corrected for endogenous T3, although it was markedly decreased when uncorrected. In hypothyroid rats, serum T3 was undetectable (>12.5 ng/100 ml), and mitochondrial α-glycerophosphate dehydrogenase activity decreased to the hypothyroid range. The DNA content was unchanged. Notably, the T3 concentration in the brain nuclear extract increased to 0.372 ± 0.206 ng/mg DNA (P < 0.02). Furthermore, the Cmax of the brain receptors increased to 380.9 ± 70.6 pg T3/mg DNA (P < 0.01), whereas the Ka decreased to 8.5 ± 0.32 × 109 M-1 (P < 0.001) even after correction for endogenous T3. The results indicate that the Cmax of the brain nuclear T3 receptors increases in hyperthyroidism, as was previously shown for liver nuclear receptors. Unlike the situation in the liver, the Cmax of the brain nuclear receptor also increased, but the Ka decreased in hypothyroidism. It is probable that brain nuclear receptors are functionally heterogeneous and that their increase together with the increase in nuclear T3 concentrations in hypothyroidism is an adaptive mechanism to accumulate the hormone and maintain cerebral function.