Thyroid hormone receptors in brain development and function

被引:482
作者
Bernal, Juan
机构
[1] UAM, CSIC, Inst Invest Biomed, Madrid 28029, Spain
[2] Inst Carlos III, CIBERER, Madrid, Spain
来源
NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM | 2007年 / 3卷 / 03期
关键词
brain development; hippocampus; nuclear receptors; thyroid hormone;
D O I
10.1038/ncpendmet0424
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Thyroid hormones are important during development of the mammalian brain, acting on migration and differentiation of neural cells, synaptogenesis, and myelination. The actions of thyroid hormones are mediated through nuclear thyroid hormone receptors (TRs) and regulation of gene expression. The purpose of this article is to review the role of TRs in brain maturation. In developing humans maternal and fetal thyroid glands provide thyroid hormones to the fetal brain, but the timing of receptor ontogeny agrees with clinical data on the importance of the maternal thyroid gland before midgestation. Several TR isoforms, which are encoded by the THRA and THRB genes, are expressed in the brain, with the most common being TR alpha 1. Deletion of TR alpha 1 in rodents is not, however, equivalent to hormone deprivation and, paradoxically, even prevents the effects of hypothyroidism. Unliganded receptor activity is, therefore, probably an important factor in causing the harmful effects of hypothyroidism. Accordingly, expression of a mutant receptor with impaired triiodothyronine (T-3) binding and dominant negative activity affected cerebellar development and motor performance. TRs are also involved in adult brain function. TR alpha 1 deletion, or expression of a dominant negative mutant receptor, induces consistent behavioral changes in adult mice, leading to severe anxiety and morphological changes in the hippocampus.
引用
收藏
页码:249 / 259
页数:11
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