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Am J Physiol Endocrinol Metab 261: E227-E232, 1991;
0193-1849/91 $5.00
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AJP - Endocrinology and Metabolism, Vol 261, Issue 2 E227-E232, Copyright © 1991 by American Physiological Society

ARTICLES

In vivo effects of flavonoid EMD 21388 on thyroid hormone secretion and metabolism in rats

J. P. Schroder-van der Elst, D. van der Heide and J. Kohrle
Department of Metabolic Diseases and Endocrinology, University Hospital, Leiden, The Netherlands.

In vitro, the synthetic flavonoid EMD 21388 appears to be a potent inhibitor of thyroxine (T4) 5'-deiodinase and diminishes binding of T4 to transthyretin. In this study, in vivo effects of long-term administration of EMD 21388 on thyroid hormone production and metabolism were investigated. Intact male rats received EMD 21388 (20 mumol.kg body wt-1.rat-1.day-1) for 14 days. [125I]T4 and 3,5,3'-[131I]triiodotyronine (T3) were infused continuously and intravenously in a double-isotope protocol for the last 10 and 7 days, respectively. EMD 21388 decreased plasma thyroid hormone concentrations, but thyrotropin levels in plasma and pituitary did not change. Plasma clearance rates for T4 and T3 increased. Thyroidal T4 secretion was diminished, but T3 secretion was elevated. Extrathyroidal T3 production by 5'-deiodination was lower. T4 concentrations were markedly lower in all tissues investigated. Total tissue T3 was lower in brown adipose tissue, brain, cerebellum, and pituitary, tissues that express the type II 5'-deiodinase isozyme due to decreased local T3 production. Most tissues showed increased tissue/plasma ratios for T4 and T3. These results indicate that this flavonoid diminished T4 and increased T3 secretion by the thyroid, probably in analogy with other natural flavonoids, by interference with one or several steps between iodide uptake, organification, and hormone synthesis.


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J. P. S.-V. D. Elst, D. Van Der Heide, H. Rokos, G. M. De Escobar, and J. Kohrle
Synthetic flavonoids cross the placenta in the rat and are found in fetal brain
Am J Physiol Endocrinol Metab, February 1, 1998; 274(2): E253 - E256.
[Abstract] [Full Text] [PDF]


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