Thyroid hormone receptors in neuronal and glial nuclei from mature rat brain

To elucidate the mechanism of thyroid hormone action in the mature brain, we analyzed nuclear T3 receptors (NT3R) in neuronal and glial nuclei. Neuronal and glial nuclear fractions were prepared from mature rat brains with about 80% and 98% purity, respectively. Results from Scatchard analyses showed that NT3R capacity in neurons was 684.2 +/- 95.4 pg T3/mg DNA (mean +/- SD) in isolated nuclei and 345.6 +/- 77.6 pg T3/mg DNA in nuclear protein extracted with 0.4 M KCl. Glial NT3R had only one eighth the capacity of neuronal receptors. Displacement studies with several T3 analogs showed highly selective affinity of the receptors for L-T3. The relative affinities for several analogs were similar to those of liver NT3R. In addition, the elution profiles of the nuclear extracts through HPLC using gel filtration or diethylaminoethyl ion exchange columns exhibited similarity between neuronal and hepatic NT3R. The receptors in neuronal and glial nuclear fractions were analyzed in three groups of rats with different T3 levels: T3 (20 micrograms/100 g BW daily, for 3 days)-injected hyperthyroid rats, intact rats, and thyroidectomized rats. There were no significant alterations in capacity or affinity of the receptors among groups. The present studies demonstrate that numerous NT3R, which seem identical to hepatic NT3R, exist in neuronal nuclei. This raises the possibility that thyroid hormone acts through binding to NT3R in the cerebral cortex of the mature rat brain.