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Background: Thyroid hormone controls a number of developmental and physiological processes in the brain by directly acting on gene expression. Transcriptome analyses in rodent identified a number of thyroid hormone regulated genes in several brain areas at different stages. Genome wide analysis of chromatin occupancy in a neural cell line also identified a subset of genes which transcription is likely to be directly regulated by thyroid hormone receptors in neurons. However, the abundance of these data and apparent discrepancies between studies brought some confusion., Results: We present here a meta-analysis of available data to identify recurrent themes in thyroid hormone action in brain cells. This provides a curated list of 734 regulated genes in rodent brain, and highlights a small number of likely direct target genes. Some of these genes are also regulated in amphibians during metamorphosis. This article is part of a Special Issue entitled: Nuclear receptors in animal development., (Copyright © 2014. Published by Elsevier B.V.)

Background: The transcriptional activity of the thyroid hormone receptors is modulated by the ligand, T3, but they have also activity as aporeceptors, in the unliganded state. Aporeceptor activity is thought to contribute to the severity of profound hypothyroidism. During development thyroid hormone receptors are expressed before onset of thyroid gland function and are present therefore in many tissues mainly as aporeceptors. The question we address is whether thyroid hormone aporeceptors are involved in physiological and/or developmental processes., Scope of Review: The scope of this article is to review the evidence for a role of thyroid hormone aporeceptors in physiology and development. Related to this topic is the activity of mutant receptors unable to bind hormone. These receptors usually have dominant negative activity. This review focuses on the wild type receptors, and does not discuss the properties of mutant receptors., Major Conclusions: Unliganded thyroid hormone receptors influence the timing and control certain aspects of amphibian pre-metamorphosis. In mammals they are likely to influence maturational processes in the brain and other organs before onset of thyroid gland function. Expression of types 2 and 3 deiodinases which control the local tissue concentration of T3 regulates the fractional receptor occupancy and therefore the relative proportion of aporeceptors. This article is part of a Special Issue entitled Thyroid hormone signalling., (Copyright © 2012 Elsevier B.V. All rights reserved.)