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The Journal of Neuroscience, May 1, 1999, 19(9):3430-3439
Expression of Type 2 Iodothyronine Deiodinase in Hypothyroid Rat
Brain Indicates an Important Role of Thyroid Hormone in the Development
of Specific Primary Sensory Systems
Ana
Guadaño-Ferraz1,
Maria José
Escámez1,
Estrella
Rausell2, and
Juan
Bernal1
1 Instituto de Investigaciones Biomédicas
"Alberto Sols," Consejo Superior de Investigaciones
Cientificas-Universidad Autónoma, and 2 Departamento
de Morfología, Universidad Autónoma de Madrid, Madrid,
Spain
Thyroid hormone is an important epigenetic factor in brain
development, acting by modulating rates of gene expression. The active
form of thyroid hormone, 3,5,3'-triiodothyronine (T3) is produced in
part by the thyroid gland but also after 5'-deiodination of thyroxine
(T4) in target tissues. In brain, ~80% of T3 is formed locally from
T4 through the activity of the 5'-deiodinase type 2 (D2), an enzyme
that is expressed mostly by glial cells, tanycytes in the third
ventricle, and astrocytes throughout the brain. D2 activity is an
important point of control of thyroid hormone action because it
increases in situations of low T4, thus preserving brain T3
concentrations. In this work, we have studied the expression of D2 by
quantitative in situ hybridization in hypothyroid
animals during postnatal development. Our hypothesis was that those
regions that are most dependent on thyroid hormone should
present selective increases of D2 as a protection against
hypothyroidism. D2 mRNA concentration was increased severalfold over
normal levels in relay nuclei and cortical targets of the primary
somatosensory and auditory pathways. The results suggest that these
pathways are specifically protected against thyroid failure and that T3 has a role in the development of these structures. At the cellular level, expression was observed mainly in glial cells, although some
interneurons of the cerebral cortex were also labeled. Therefore, the
T3 target cells, mostly neurons, are dependent on local astrocytes for
T3 supply.
Key words:
thyroid hormones; deiodinases; astrocytes; barrel field; somatosensory system; auditory system; thalamus
Copyright © 1999 Society for Neuroscience 0270-6474/99/1993430-10$05.00/0
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