Sequential Changes in the Nuclear Triiodothyronine Receptors and Mitochondrial α-Glycerophosphate Dehydrogenase Activity after the Administration of Triiodothyronine

Abstract

The dynamics of the induction of nuclear triiodothyronine (T3)-receptors and mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) were studied in rat liver after a single injection of a large amount of T3. The maximal binding capacity (Cmax) and association constant (Ka) of the nuclear receptors were determined by Scatchard analyses with and without correction for endogenous T3 measured by radioimmunoassay. It was demonstrated that the administration of T3 induced sequential increases in the number of nuclear T3-receptors and alpha-GPD activity in the liver. The nuclear receptors were rapidly increased to 2.5 times the hypothyroid level and thereafter decreased with a half-life of about 2 days. A parallel change in alpha-GPD activity was noted after a lag period. The total amount of extracted nuclear proteins in the liver was increased 3 days after the administration of T3. It seems likely, therefore, that the T3-induced increase in nuclear receptors is responsible, at least in part, for the induction of this enzyme. The possibility is also suggested that the nuclear receptors may be a nonhistone protein selectively synthesized in an early stage of the hormonal stimulation. Following the injection of T3, marked changes in apparent Ka were seen when no correction was made for the amount of endogenous T3 bound to the extracted nuclear proteins. With the correction, however, Ka remained the same despite the changes in the nuclear receptors and enzyme activity. The results obtained provide further evidence for the hormonal modulation of the nuclear receptors which is closely linked with the hormonal effect.