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Título:	Different tissue distribution, elimination, and kinetics of thyroxine and its conformational analog, the synthetic flavonoid EMD 49209 in the rat
Autor:	Schröder-van der Elst, Janny P.; Heide, Daan van der; Morreale de Escobar, Gabriella CSIC
Fecha de publicación:	ene-1997
Editor:	Endocrine Society
Citación:	Endocrinology 138(1): 79-84 (1997)
Resumen:	The synthetic flavonoids EMD 23188 and EMD 49209, developed as T4 analogs, displace T4 from transthyretin, and in vitro they inhibit 5'-deiodinase activity. In vivo EMD 21388 causes tissue-specific changes in thyroid hormone metabolism. In tissues that are dependent on T3 locally produced from T4, total T3 was diminished. It was not known whether it was the presence of EMD interfering with 5'-deiodinase type II in tissues or the decreased T4 (substrate) availability that caused the lowered T3. To study whether the flavonoids enter tissues and, if this were the case, whether they enter tissues similarly, [125I]EMD 49209 together with [131I]T4 were injected into female rats and rats pretreated with EMD 21388. Tissues were extracted and submitted to HPLC. [125I]EMD 49209 disappeared quickly from plasma and enters peripheral tissues; peak values were reached after 0.25-0.5 h. Then [125I]EMD 49209 appeared in the intestines (after 6 h 40% of the dose). Tissue uptake of [131I]T4 was very rapid. EMD 21388 pretreatment caused an increase in the excretion of [125I]EMD 49209 into the intestines (40% after 0.25 h). The uptake of [131I]T4 increased, but not high enough to ensure normal tissue T4 concentrations. In the 5'-deiodinase type II-expressing tissues, no [125I]EMD 49209 could be detected. We conclude that the decrease in T3 locally produced from T4 is caused by the shortage of T4 as substrate and not to a direct effect of EMD on the activity of 5'-deiodinases I and II.
Descripción:	6 pages, 2 figures, 3 tables.-- et al.
Versión del editor:	http://endo.endojournals.org/cgi/content/abstract/138/1/79
URI:	http://hdl.handle.net/10261/24104
ISSN:	0013-7227
Aparece en las colecciones:	(IIBM) Artículos