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This version published online on February 2, 2006
Endocrinology, doi:10.1210/en.2005-1325
A more recent version of this article appeared on May 1, 2006
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*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*IODINE
*LEVOTHYROXINE
*LIOTHYRONINE

Submitted on October 18, 2005
Accepted on January 23, 2006

Mechanisms of adaptation to iodine deficiency in rats: Thyroid status is tissue-specific. Its relevance for man

Pablo Enrique Pedraza, Maria-Jesus Obregon, Hector Francisco Escobar-Morreale, Francisco Escobar del Rey, and Gabriella Morreale de Escobar*

Endocrinología Molecular, Instituto de Investigaciones Biomédicas, Centro mixto Alberto Sols, Consejo Superior de Investigaciones Científicas and Facultad de Medicina, Universidad Autónoma de Madrid, 28029-Madrid (Spain)

* To whom correspondence should be addressed. E-mail: gmorreale{at}iib.uam.es.

Many animals, man included, live in areas providing insufficient iodine (I) for optimal health. Degrees of I deficiency (ID) vary from mild-moderate to very severe, with quali- and quanti-tatively different negative consequences.

To understand the mechanisms involved in adaptation to different grades of ID, we fed rats a low iodine diet, plus additions resulting in a 250-fold range of I daily available to the thyroid, ranging from 5 µg (adequate) down to 0.02 µg I. We measured thyroid weight, total I, T4, T3 and type I 5' iodothyronine deiodinase (D1) activity, TSH, T4, FT4. and T3 in plasma, T4 and T3 in eleven tissues, and two 5' deiodinase isoenzymes in four.

TSH-independent thyroid autoregulation plays an important role in addition to TSH-dependent mechanisms in the adaptation to ID, avoiding a decrease of T3 in plasma and most tissues, despite a marked decrease of plasma T4, whereas extra-thyroidal responses of D2 mitigate T3-deficiency in tissues where T3 is mostly generated from T4. We have focused on mild and moderate ID, the least investigated experimentally, despite its current frequency in industrialized countries. The novel and important finding of our study is that thyroid status cannot be defined for the animal as a whole: at all grades of ID, T3 is simultaneously elevated, normal and low in different tissues.

Present findings in mild-moderate ID draw attention to the importance, for man, of the resulting hypothyroxinemia, that may affect mental functions and neurodevelopment of the inhabitants, even when they do not have the increased TSH or clinical hypothyroidism, often wrongly attributed to them.


Key words: Thyroid autoregulation • hypothyroxinemia • graded iodine availability




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