Conversion of thyroxine to 3,5,3'-triiodothyronine in several rat tissues in vivo: the effect of hypothyroidism

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Abstract
The local conversion of thyroxine (T4) to 3,5,3'-triiodothyronine (T3) has been recognized as a source of T3 at various sites in euthyroid rats. The present study was designed to evaluate the effect of hypothyroidism on the source and quantity of T3 at several of these sites (liver, cerebral cortex (Cx), thymus, testis, brown adipose tissue). For this purpose intact euthyroid rats and radiothyroidectomized (RTx) rats received a continuous iv infusion of [125I]T4 and [131I]T3 until isotopic equilibrium was attained. In addition to the labelled iodothyronines, RTx rats received a continuous iv infusion of 0.75 μg T4/day, in order to maintain a defined hypothyroid state. At the end of the infusion period the animals were bled and perfused, and homogenates of the various organs were prepared. The mean plasma T4 and T3 levels in T4-maintained RTx rats, as measured by RIA, were 1.5 μg/dl and 15 ng/dl (euthyroid values: 5.2 μg/dl and 48 μg/dl, respectively). The plasma and tissue homogenates were processed for thin layer chromatography and the [125I]T4, [125I]T3 and [131I]T3 levels determined. From these data the concentrations of T4, total T3 and T3 derived from local T4 to T3 conversion (LcT3(T4)) in tissue could be calculated. The relative mean contribution of LcT3(T4) to the total T3 in Cx (75%), thymus (31%), testis (43%) and brown adipose tissue (65%) from hypothyroid rats was higher than that determined for euthyroid animals (66%, 19%, 29% and 27%, respectively). The reverse was found for the liver (15% vs 39%). As a consequence, hypothyroidism led to a substantial loss of intracellular T3 in the liver (about 80%), whereas in all other tissues investigated the decrease in total T3 was less. In spite of the low intracellular T4 levels in hypothyroid rats, the quantity of LcT3(T4) in brown adipose tissue had increased significantly. This was not the case in the other tissues investigated. However, as found for brown adipose tissue, the ratio between LcT3(T4) and T4 found for Cx, thymus and (although not statistically significant) testis was higher in hypothyroid rats than in euthyroid animals, again suggesting a higher degree of in vivo T4 to T3 conversion in the hypothyroid state. These results strongly suggest that local factors play an important role in the regulation of intracellular T3 levels.

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