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Effects of Dexamethasone on Kinetics and Distribution of Triiodothyronine in the Rat^*

Nuclear Medicine Service, Veterans Administration Medical Center San Francisco, California 94121
The Departments of Medicine and Radiology, University of California San Francisco, California 94121

Address all correspondence and requests for reprints to: Dr. Ralph R. Cavalieri, Nuclear Medicine Service (115), Veterans Administration Medical Center, 4150 Clement Street, San Francisco, California 94121.

Abstract

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 µg/day·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·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·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· 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. Serum binding is diminished, and net cellular binding of T₃ is decreased to an even greater degree. The MCR of T₃ is reduced to about the same extent as its production rate, so the circulating level of T₃ is unaltered. (Endocrinology 114: 215, 1984)

Footnotes

^* A part of this work was presented at the 64th Meeting of The Endocrine Society, San Francisco, CA, 1982, and at the 58th Meeting of the American Thyroid Association, Quebec City, 1982. This work was supported by the V.A. Research Service.

Received March 17, 1983.

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