TRI-IODOTHYRONINE-INDUCED INCREASE IN RAT-LIVER NUCLEAR THYROID-HORMONE RECEPTORS ASSOCIATED WITH INCREASED MITOCHONDRIAL ALPHA-GLYCEROPHOSPHATE DEHYDROGENASE-ACTIVITY

The effect of tri-iodothyronine injection on the nuclear tri-iodothyronine receptor (putative thyroid-hormone receptor) was examined in rat liver. Nuclear receptors were extracted from isolated nuclei with 0.4 M-KCl, and their association constants [K(a)] and maximal binding capacities [C(max)] were determined by Scatchard analyses with and without correction for the endogenous hormone. The amount of endogenous tri-iodothyronine bound to non-histone protein was estimated on the basis of the specific radioactivity of [125I]tri-iodothyronine injected 2 h before the rats were killed. It was demonstrated that C(max.) of the nuclear receptors was 2.5-fold higher in severely hyperthyroid than in hypothyroid rats. However, irrespective of the thyroid status, the K(a) of the receptors remained unchanged when corrected for endogenous tri-iodothyronine bound to non-histone protein. The validity of the correction was supported by experiments in vitro in which nuclear receptors were preincubated with unlabelled tri-iodothyronine. The increase in C(max.) of nuclear receptors was directly related to mitochondrial α-glycerophosphate dehydrogenase activity. These results suggest a hormonal modulation of the nuclear receptors which is associated with hormonal action.