Concentrations of thyroxine and 3,5,3'-triiodothyronine at 34 different sites in euthyroid rats as determined by an isotopic equilibrium technique.

Abstract

The present study was designed to assess the quantities of T4 and T3, and the source (i.e. plasma-derived vs. locally produced) of the latter iodothyronine, in various rat tissues. For this purpose, normal intact rats were brought to isotopic equilibrium by means of a continuous iv infusion of [125I]T4 and [131I]T3 for a prolonged period. At the end of the infusion period, the animals were bled and perfused. Either whole small organs or weighed portions of tissues were homogenized in saline. The iodothyronines were extracted with ethanol-ammonia and separated by TLC. The [125I]T3/[131I]T3 ratios for the tissue homogenates and plasma were determined, and the relative contribution of the T3 derived from local T4 to T3 conversion [abbreviated: Lc T3 (T4)] to the total T3 in a given tissue was calculated. The endogenous T4 and T3 levels in the various organs were computed from the known specific activities of the labeled iodothyronines. The concentration of T4 in plasma greatly exceeded that found for tissue. Among the tissues examined, the T4 concentration was highest in the liver and lowest in cerebral cortex and cerebellum. T3 (per gram) was most abundant in the kidney and anterior pituitary gland and least abundant in the testis, epididymis, and erythrocytes. In contrast to the other tissues investigated, the concentration of T3 in several regions of the brain and anterior pituitary gland either equalled or exceeded that of T4. Plasma exhibited by far the lowest T3/T4 ratio. For most of the organs investigated the contribution of Lc T3(T4) appeared to be low. On the other hand, in 15 tissues, including the central nervous system, the local production of T3 accounted for one fifth or more of the total T3 content. Although there were no regional differences between the total T3 levels in the brain, the relative contribution of Lc T3(T4) was 65% in the cerebral cortex and only 22% in the spinal cord. The variation in the source of T3 in the various parts of the central nervous system may be related to regional differences in T4 and T3 metabolism. The fact that the present study demonstrates that the relationship between circulating T3 and intracellular T3 varies from one organ to the next may be important for accurate interpretation of plasma T4 and T3 levels and for designing optimal thyroid hormone replacement therapy for patients with hypothyroidism.