The contribution of local thyroxine monodeiodination to intracellular 3,5, 3'-triiodothyronine in several tissues of hyperthyroid rats at isotopic equilibrium.

Abstract

The local conversion of T4 as a source of intracellular T3 in several organs of both hypothyroid and euthyroid rats has recently been recognized to be an important phenomenon. In the present study the source and quantity of T3 in various peripheral tissues of hyperthyroid rats were investigated. Athyreotic rats received a continuous iv infusion of 3.5 micrograms T4/100 g BW X day over a prolonged period in order to attain hyperthyroid conditions. At the same time, the animals also received a continuous iv infusion of [125I]T4 and [131I]T3 until isotopic equilibrium was achieved. After the animals were bled and perfused, the source and quantity of T3 in various tissue homogenates and subcellular preparations of liver, kidney, and the anterior pituitary gland were analyzed. In spite of the elevated plasma T3 and T4 levels, the concentration of T3 in the cerebral cortex and cerebellum was within the normal range. The contribution of T3 derived from local T4 to T3 conversion [Lc T3(T4)] was rather low in both parts of the brain (cerebral cortex, 26%; cerebellum, 15%) when compared with values previously determined for euthyroid rats (cerebral cortex, 67%; cerebellum, 50%). It is concluded that in the cerebral cortex and cerebellum of hyperthyroid rats normal T3 concentrations were maintained by a compensatory decrease in the degree of Lc T3(T4). Whereas previous studies revealed that Lc T3(T4) contributes significantly to the T3 in the pituitary glands of both hypothyroid and euthyroid rats, this was not the case for the hyperthyroid animals; virtually all T3 was derived from plasma. The elevated plasma T3 levels caused an increased T3 content in both the homogenate and the nuclear fraction, leading to plasma TSH levels which were below the detection limit. It was found that the T3 in muscle was derived exclusively from plasma. Both the liver and kidney showed high concentrations of T3. Whereas Lc T3(T4) was the main source of T3 in the liver, it contributed only a minor fraction of the total T3 content in the kidney. In the liver Lc T3(T4) accounted for 50-53% of the T3 content in the mitochondrial and cytosolic fractions and about 64% in the microsomal fraction. In the kidney there was a small, but significant, amount of Lc T3(T4) in these subcellular fractions. In contrast, in the hepatic nuclei only 13% of the T3 was attributable to Lc T3(T4), whereas no Lc T3(T4) could be detected in the renal nuclei.