Toshihiko Yokota

Triiodothyronine effects on RNA polymerase activities in isolated neuronal and glial nuclei of the mature rat brain cortex

Our previous study demonstrated that a high level of nuclear triiodothyronine receptors (NT3R), which are identical to the hepatic NT3R, exists in neuronal nuclei of the cerebral cortex from an adult rat brain. To investigate whether thyroid hormone acts through binding to nuclear receptors, we measured RNA polymerase activities in isolated neuronal and glial nuclei of cerebral cortices prepared from three groups of rats with different T3 levels: T3 (20 micrograms/100 g BW/d, for three days)-injected hyperthyroid rats, control normal rats, and thyroidectomized rats. The enzyme activities in both nuclear fractions were assayed under the condition of dose-response linearity. When RNA polymerase I activity in neuronal nuclei from control rats was expressed as 100%, the activities from T3-injected and hypothyroid rats were 112.3 +/- 3.4% (n = 5, P less than .05) and 86.9 +/- 3.5% (n = 5, P less than .05), respectively. The increase in the enzyme activities were parallel to the increase in T3 content in neuronal nuclei among the groups. Glial nuclear RNA polymerase I showed the same tendency in response to T3, although the enzyme activity was smaller than from neuronal nuclei. RNA polymerase II, however, showed no significant change in response to altered T3 levels. The existence of numerous receptors and an induction of increased RNA polymerase I activity by T3 in neuronal nuclei raise the possibility that thyroid hormone through a NT3R pathway in the cerebral cortex of even the mature rat brain.

Clinical significance of elevated labeled TSH binding (LTB) activity in sera of patients with Graves' disease and other thyroid disorders

Labeled TSH binding (LTB) of individual serum samples was monitored simultaneously using the thyrotropin binding inhibitor immunoglobulin (TBII) assay. In 643 TBII determinations, 86 sera (13.4%) showed elevated LTB. The incidence of elevated LTB in active Graves’ patients (17.5%) was much higher than that of inactive Graves’ patients (6.7%). After TBII activities were corrected by LTB, 79% of the active Graves’ patients who had negative raw TBII were found to be positive. In patients with untreated active Graves’ disease, the detectability of TBII increased from 85% to 91% after LTB correction, while those in inactive Graves’ and other thyroid disorders did not increase so much (1.6 and 0%, respectively). Further, most of elevated LTB seen in other thyroid disorders were found to be different from those in Graves’ disease by heat stability experiment. Serial observations of LTB and TBII in 24 Graves’ patients showed 2 patterns. Parallel alterations were observed in 13 patients and reciprocal alterations in 11 patients. Patients showing parallel alteration had smaller goiter and were more sensitive to antithyroid drugs than those showing the latter pattern.