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.

Abstract

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, approximately 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.

• Authors: A Guadaño-Ferraz, M J Escámez, E Rausell, J Bernal
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 19 Issue 9 Pg. 3430-9 (May 01 1999) ISSN: 0270-6474 [Print] United States
• PMID: 10212303 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calbindins
• Nerve Tissue Proteins
• RNA, Messenger
• S100 Calcium Binding Protein G
• Thyroid Hormones
• iodothyronine deiodinase type II
• Iodide Peroxidase

Topics

• Animals
• Astrocytes (enzymology)
• Auditory Pathways (enzymology)
• Brain (enzymology)
• Calbindins
• Cerebral Ventricles (enzymology)
• Female
• Gene Expression Regulation, Enzymologic (physiology)
• Hypothyroidism (enzymology)
• In Situ Hybridization
• Iodide Peroxidase (genetics, metabolism)
• Nerve Tissue Proteins (analysis)
• Neuroglia (enzymology)
• Pregnancy
• RNA, Messenger (analysis)
• Rats
• Rats, Wistar
• S100 Calcium Binding Protein G (analysis)
• Somatosensory Cortex (enzymology)
• Thyroid Gland (physiology, physiopathology)
• Thyroid Hormones (physiology)
• Transcription, Genetic