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Sequential changes in rat liver nuclear tri-iodothyronine receptors and mitochondrial alpha-glycerophosphate dehydrogenase activity after administration of tri-iodothyronine.

ABSTRACT: The dynamics of the induction of nuclear tri-iodothyronine receptors and mitochondrial alpha-glycerophosphate dehydrogenase were studied in rat liver after a single injection of tri-iodothyronine. The maximal binding capacity (C(max.)) and association constant (K(a)) of the nuclear receptors were determined by Scatchard analyses with and without correction for the endogenous tri-iodothyronine measured by radioimmunoassay. The administration of tri-iodothyronine induced sequential increases in the concentration of nuclear receptors and alpha-glycerophosphate dehydrogenase activity in the liver. The nuclear-receptor concentration was increased to 2.5 times that in the hypothyroid rat 1 day after the administration of hormone, and then decreased, with a half-life of about 2 days. alpha-Glycerophosphate dehydrogenase activity changed in parallel with the nuclear-receptor concentration, showing a delayed response. The total amount of non-histone protein in the liver was significantly increased 3 days after the administration. It seems likely therefore that the tri-iodothyronine-induced increase in nuclear-receptor concentration is responsible, at least in part, for the induction of this enzyme. The possibility is also suggested that nuclear receptors may be one of the non-histone proteins selectively synthesized at an early stage of the hormonal stimulation. Throughout the time course, the K(a) values of the nuclear receptors for tri-iodothyronine remained unchanged, when corrected for endogenous tri-iodothyronine bound to the non-histone proteins, although they were apparently changed when the correction was not made. The results obtained provide further evidence for hormonal modulation of the nuclear receptors which is closely linked with the hormonal effect.

SUBMITTER: Nakamura H

PROVIDER: S-EPMC1161318 | biostudies-other | 1979 Aug

REPOSITORIES: biostudies-other

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Project description:The possibility that thyroxine (T4) itself exerts the hormonal effect in vivo on the rat liver nuclear receptor was studied with the aid of iopanoic acid (IOP), an inhibitor of the conversion of T4 into tri-iodothyronine (T3). After administration of 2.4 micrograms of T4/100 g body weight to hypothyroid rats for 7 days, T4 and T3 concentrations in serum and in the liver nuclear non-histone protein (NHP) were all increased to the hyperthyroid range. Hepatic mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) activity and DNA content increased significantly. The equilibrium association constant (Ka) of the nuclear T3 receptor was unchanged and the maximal binding capacity (Cmax.) increased 1.4-fold. Simultaneous administration of IOP (5 mg/100 g body weight) to the rats given 2.4 micrograms of T4/100 g body weight completely blocked the conversion into T3. The serum T4 was even more increased, whereas the serum T3 decreased to the hypothyroid range. Although the NHP-bound T4 was at a concentration comparable with the rats given T4 alone, no NHP-bound T3 was detected. Yet the alpha-GPD activity was elevated 2.8-fold and the DNA content increased to the same extent as observed in the rats given T4 alone. The Ka and Cmax. of the nuclear receptor were significantly decreased. After administration of 48 or 480 micrograms of T4/100 g body weight for 3 days, serum T4 and T3 were markedly increased. The NHP-bound T3 was also increased, but no NHP-bound T4 was detected. The alpha-GPD activity was markedly elevated, but the DNA content was unchanged. The Cmax. per g of liver was increased, whereas the Ka remained unchanged. Simultaneous administration of IOP to these animals could not completely block the T4 conversion. The observed hormonal effects in the absence of nuclear T3 indicate that T4 possesses the intrinsic hormonal activities on the rat liver. T4 is less potent in induction of alpha-GPD activity but as potent in increment of hepatic DNA as T3. Although the binding site for T4 is not fully characterized, it appears to be acidic NHP. T4 is an active hormone, yet is also a prohormone of T3, offering the closest analogy with testosterone.

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Sequential changes in rat liver nuclear tri-iodothyronine receptors and mitochondrial alpha-glycerophosphate dehydrogenase activity after administration of tri-iodothyronine.

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