Sources and quantity of 3,5,3'-triiodothyronine in several tissues of the rat.

Abstract

A B S T R A C T The local conversion of thyroxine (T4), which is an important source of intracellular 3,5,3'-triiodothyronine (T3) in several rat tissues, has been subject of recent investigations. In the present study the regulation of this phenomenon in vivo was investigated in various peripheral tissues of the rat.Intact euthyroid and radiothyroidectomized (Tx) rats received a continuous intravenous infusion of [125I]T4 and ['31I]T3 until isotope equilibrium was attained. In addition to the labeled iodothyronines, Tx rats received a continuous intravenous infusion of 0.2 or 1.0 ,g carrier T4/100 g body wt per d, to create hypothyroid or slightly hypothyroid conditions, respectively. After the animals were bled and perfused the contribution of T3 derived from local conversion of T4 to T3 [Lc T3(T4)] to the total T3 in homogenates from several tissues and subcellular fractions from the liver, kidney, and anterior pituitary gland could be calculated. In all experiments T3 in muscle was derived exclusively from the plasma. In the cerebral cortex and cerebellum, however, most of the intracellular T3 was derived from the intracellular conversion of T4 to T3. It is demonstrated that for hypothyroid rats an increased relative contribution of Lc T3(T4) reduced the loss of total T3 in the brain. This phenomenon was also encountered for the anterior pituitary gland, although in this tissue the proportion of the total tissue T3, contributed by locally produced T3 was considerably lower than the values found for the cerebral cortex and cerebellum in all experiments.The present findings, regarding the source and quantity of pituitary nuclear T3 strongly suggest that both plasma T3 and T4 (through its local conversion into T3) play a role in the regulation of thyrotropin secretion. The contribution of Lc T3(T4) to the total pituitary nuclear T3 was of minor importance in euReceived for publication 23 August 1982 and in revised form 11 July 1983. thyroid rats (-20%), compared with that found for both groups in T4-supplemented athyreotic rats (-40%).The total T3 concentration in the liver decreased from euthyroid to hypothyroid rats and was associated with a decrease in the tissue/plasma T3 concentration gradient. A minor proportion of hepatic T3 was contributed by Lc T3(T4), which in fact decreased significantly from the euthyroid to the hypothyroid state. In contrast to other subcellular fractions from the liver, no Lc T3(T4) could be demonstrated in the nuclear fraction. It is suggested that the liver plays an important role with respect to regulation of the circulating T3 concentration.In the kidney, a very small proportion of the total T3 was derived from locally produced T3 in all experiments (4-7%). As found in the liver, all nuclear T3 appeared to be derived from the plasma. In contrast to the liver, subcellular T3 pools in the kidney seemed to be exchangeable.

Type II iodothyronine deiodinase provides intracellular 3,5,3′-triiodothyronine to normal and regenerating mouse skeletal muscle

“…The contribution of each to receptor occupancy varies among different tissues. The nuclear T 3 in tissues not expressing D2, such as the D1-expressing liver and kidney, is almost exclusively T 3 (T 3 ) (1,10,27). The importance of the distinction between the two sources is that T 3 (T 4 ) production can be regulated in specific cells or tissues by various pathways such as cyclic AMP or FoxO3, in addition to being negatively regulated by T 3 (transcriptionally) or T 4 (postranslationally), whereas T 3 (T 3 ) is regulated by the hypothalamic-pituitary-thyroid axis (1,3,4,6).…”

Role of sodium in thyroid hormone uptake by rat skeletal muscle.

“…Previous studies in our laboratory demonstrated that part of the 3,5,3'-triiodo-L-thyronine (T3)' entering skeletal muscle cells does so by a stereo-specific and energy-and temperature-dependent process (10). In this tissue the nuclear-associated T3 derives almost exclusively from circulating T3 (11) without contribution from the intracellular 5'-deoidination of thyroxine (T4), thus indicating that the plasma membrane might modulate the availability of active thyroid hormone. However, the exact mechanism of thyroid hormone entry into cells is still poorly defined.…”

Thyroid hormone uptake in cultured rat anterior pituitary cells: effects of energy status and bilirubin

“…The nuclear-bound T 3 in the pituitary is partly derived from the plasma T 3 and partly from intracellular conversion of T 4 to T 3 by type II deiodinase (Van Doorn et al 1984), and the presence of type II but not type I deiodinase activity in cultured anterior pituitary cells has been reported (Everts et al 1995b). Because type II deiodinase activity was diminished even in the pituitary of fasted rats (St Germain & Galton 1985), a normal intracellular T 3 concentration could be maintained only if transport of thyroid hormone into the pituitary were enhanced.…”