title: The effect of propylthiouracil and methimazole on the peripheral conversion of thyroxine to 3,5,3'-triiodothyronine in athyreotic thyroxine-maintained rats.
abstract: The effect of prolonged oral administration of PTU and MMI on the local conversion of T4 to T3 was studied in T4-maintained athyreotic rats. For this purpose the rats were equilibrated with [125I]T4 and [131I]T3 by means of continuous iv infusions. PTU treatment reduced the MCR of both T4 and T3, as well as the T3 levels in plasma, muscle, liver, kidney and cerebellum. In the cerebral cortex the total intracellular T3 concentration was not affected, while in the pituitary it even increased. The amount of T3 derived from local conversion of T4 to T3 (LcT3(T4)) was reduced in the liver. PTU treatment did not influence Lc T3(T4) in the cerebellum, but did cause an increase in the amount of T3 derived from this source in the cerebral cortex and the pituitary gland (both the homogenate and the nuclear fraction). The results indicate that in contrast to that in liver, local T3 production in the brain and pituitary must occur predominantly via a pathway which is not inhibited by PTU. In MMI-treated rats the total T3 concentration in the cerebral cortex and cerebellum was not altered, whereas both the MCR of T3 and the T3 levels in plasma and various other tissues were elevated. The relative contribution of Lc T3(T4) increased in liver and was reduced in the cerebral cortex, cerebellum and pituitary gland. In all experiments in liver the contribution of Lc T3(T4) to nuclear T3 was negligible, whereas this was not the case for the other hepatic subcellular fractions. As in liver, virtually all renal nuclear T3 was derived from plasma. The present findings suggest that the production of T3 in liver and kidney, and its subsequent release into the blood, may provide a mechanism for the regulation of plasma T3 levels but is not a direct source of their nuclear T3. In the pituitary gland and the brain local T4 to T3 conversion functions as a source of T3 for the control of local utilization. In this respect the maintainance of constant T3 levels in the brain might be important. These differences among tissues suggest that different mechanisms are involved in T4 5'-deiodination.
mesh_terms: D000818:Animals; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008713:Methimazole / Q000494:pharmacology*; D011441:Propylthiouracil / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013965:Thyroidectomy; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D014284:Triiodothyronine; D008713:Methimazole; D011441:Propylthiouracil; D013974:Thyroxine