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

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 (C_max) and equilibrium association constant (K_a) 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 C_max 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 K_a 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 C_max 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 C_max of the brain nuclear T₃ receptors increases in hyperthyroidism, as was previously shown for liver nuclear receptors. Unlike the situation in the liver, the C_max of the brain nuclear receptor also increased, but the K_a 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.