Abstract
Although 3,5,3′-triiodothyronine (T3) is considered to be the primary bioactive thyroid hormone (TH) due to its high affinity for TH nuclear receptors (TRs), new data suggest that 3,5-diiodothyronine (T2) can also regulate transcriptional networks. To determine the functional relevance of these bioactive THs, RNA-seq analysis was conducted in the cerebellum, thalamus-pituitary and liver of tilapia treated with equimolar doses of T2 or T3. We identified a total of 169, 154 and 2863 genes that were TH-responsive (FDR < 0.05) in the tilapia cerebellum, thalamus-pituitary and liver, respectively. Among these, 130, 96 and 349 genes were uniquely regulated by T3, whereas 22, 40 and 929 were exclusively regulated by T2 under our experimental paradigm. The expression profiles in response to TH treatment were tissue-specific, and the diversity of regulated genes also resulted in a variety of different pathways being affected by T2 and T3. T2 regulated gene networks associated with cell signalling and transcriptional pathways, while T3 regulated pathways related to cell signalling, the immune system, and lipid metabolism. Overall, the present work highlights the relevance of T2 as a key bioactive hormone, and reveals some of the different functional strategies that underpin TH pleiotropy.
Highlights
Thyroid hormones (THs) are endocrine messengers that are well known for their pleiotropic physiological effects in vertebrates
Thalamus-pituitary and liver of tilapia that were treated with equimolar doses of T2 or T3 (25 nM) per 12 h were sequenced using the Illumina GAIIx platform
We previously showed that this hormone concentration and exposure period does not induce an hyperthyroidal state[8]
Summary
Thyroid hormones (THs) are endocrine messengers that are well known for their pleiotropic physiological effects in vertebrates. THs can exert non-genomic effects via membrane bound receptors, they primarily act on the genome by binding with their nuclear receptors (TRs), which function as ligand-dependent transcription factors. This in turn, induces the expression of TH-regulated genes. Aside from its well-studied non-genomic effects[6,7], previous data in teleosts[5,8] and murine models[9,10] have shown that 3,5-di-iodothyronine (T2), a product of T3 outer-ring deiodination, is a transcriptionally bioactive hormone Despite this fact, it is greatly understudied when compared to T3. T2 regulates gene sets that are involved in pathways that affect particular biological processes, emphasizing its non-redundant role in teleostean physiology
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