Carrier-Mediated Transport of Thyroid Hormone (TH) into Rat Hepatocytes is Rate Limiting in Total Cellular Uptake and Metabolism
TH has a wide spectrum of activities on several tissues, most importantly those related to the economy of energy production and expenditure. The main secretory product of the thyroid, thyroxine (T4) has little, if any, intrinsic metabolic activity (1). Most of the in vivo effects of T4 can be explained by its conversion to 3,3′,5-triiodothyronine (T3) in peripheral tissues (2). Another product of the peripheral deiodination of T4 is the biologically inert 3,3′,5′-triiodothyronine (reverse T3, rT3) (3). Normally, extrathyroidal conversion accounts for approximately 80% of total T3 production and an even greater fraction of total rT3 production in humans, as well as in rats (4,5). Most of the action of T3 is initiated by binding to a nuclear, chromatic-associated receptor (6), although direct effects on mitochondria (7) and plasma membranes (8–10) have also been reported. Recent studies have pointed to differences between tissues with regard to the origin of nuclear T3 (11). Thus, in the pituitary 50% and in the central nervous system 80% of nuclear T3 is derived from local T4 → T3 conversion, the remainder being taken up from the circulation. Probably due to the rapid exchange between the plasma and tissue compartments, most of nuclear T3 in the liver and the kidneys is derived from the circulation with a negligible contribution from local T4 → T3 conversion (11,12), despite the fact that the latter tissues are more important sites for the total body production of T3 (13). Thus, passage of T4 and T3 through the plasma membrane plays an important part in the ultimate delivery of T3 to nuclear receptors.
KeywordsThyroid Hormone FEBS Letter Free Hormone Peripheral Deiodination Conjugate Accumulation
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