Effects of dexamethasone on kinetics and distribution of triiodothyronine in the rat.
Studies were designed to examine the effects of the glucocorticoid dexamethasone (Dex) on the distribution and turnover of T3 separately from its effects on the pituitary and thyroid. Male Sprague-Dawley rats (200-250 g) were surgically thyroidectomized and given a replacement dose of T4 (1.6 micrograms/day X 100 g BW) throughout the experiment via a sc implanted osmotic minipump. Six or 7 days after starting the T4 infusion, each animal was given [125I]T3 by constant infusion (via a second minipump) for 5 or 6 days and, during the final 5 days, either Dex (0.15 mg/day X 100 g) or saline in a third minipump. Methanol extracts of serum and tissues removed at the end of the infusion were analyzed for [125I]T3 concentration by high performance liquid chromatography. The MCR, computed from the infusion rate of tracer and the serum concentration of [125I]T3 at the end of the infusion, averaged 25.7 +/- 1.3 (+/-SE) ml/h X 100 g in the controls and 15.1 +/- 2.6 in the Dex-treated rats. Serum T3 (RIA) concentrations were similar in the two groups. The plasma T3 production rate was decreased from 9.51 +/- 1.14 ng/h X 100 g in controls to 5.13 +/- 1.16 in the Dex-treated animals. The fraction of administered T4 converted to T3 was reduced from 0.21 to 0.11 by Dex treatment. Tissue to serum (T/S) [125I]T3 concentration ratios were significantly decreased by Dex to approximately 50% of the control value in each of the tissues sampled (liver, kidney, and skeletal muscle). The reduction in the T/S ratio could not be attributed to an increase in the net serum binding of T3; in fact, serum hormone binding was diminished by Dex treatment. The distribution data indicate that net tissue binding of T3 in these organs is reduced to an even greater extent than is serum binding of T3. The glucocorticoid-induced fall in T3 MCR could be accounted for by the decrease in T/S ratios, the latter being a measure of T3 distribution volume in the tissues studied. The rate of T4 5'-deiodination in vitro was diminished in homogenates of livers from Dex-treated animals when the incubation was performed with and without added thiol as cofactor, indicating that the hepatic level of active T4 5'-deiodinase is reduced by Dex. Thus, Dex causes multiple alterations in T3 metabolism. Total body T3 production from T4 in extrathyroid sites, and in the liver in particular, is reduced.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D007453:Iodide Peroxidase / Q000378:metabolism; D007457:Iodine Radioisotopes; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013974:Thyroxine / Q000097:blood / Q000378:metabolism; D014284:Triiodothyronine / Q000097:blood / Q000378:metabolism*
D007457:Iodine Radioisotopes; D014284:Triiodothyronine; D003907:Dexamethasone; D007453:Iodide Peroxidase; D013974:Thyroxine