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Thyroid Hormone Signaling and Function: News from Classical and Emerging...
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Thyroid Hormone Signaling and Function: News from Classical and Emerging Models

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling".

Deadline for manuscript submissions: closed (1 July 2021) | Viewed by 21021

Special Issue Editors

Dr. Michelina Plateroti

E-Mail Website
Guest Editor
Cancer Research Center of Lyon, UMR Inserm 1052 - CNRS 5286 – CLB, 28 rue Laennec, 69373 Lyon, France
Interests: intestine; stem cells; cancer stem cells; thyroid hormones; thyroid hormone nuclear receptors
Dr. Maria Sirakov

E-Mail Website
Guest Editor
Researcher, Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Napoli, Italy
Interests: developmental biology; functional genomics; stem cell biology; TH signaling pathway

Special Issue Information

Dear Colleagues,

Thyroid hormones (THs) play pleiotropic roles in the development and the homeostasis of several organs in vertebrates. Their actions depend, at the cellular level, on thyroid hormone nuclear receptors (TRs), which are transcription factors whose activity is modulated by the active form of the hormone, T3.

The importance of THs and their receptors to regulate development and homeostasis in different cellular and/or tissue contexts in vertebrates strongly suggests that they may play an important role in stem cell biology and in cell fate. These functions could be played by TH signaling alone or through cross-interaction with other developmental signaling pathways such as Notch, Wnt, or BMP. Interestingly, these pathways are dysregulated in degenerative diseases such as cancer.

The presence of orthologs of the thyroid gland and of TR genes have been described in several vertebrates and non-vertebrate species; their conservation shows the importance of the TH–TR interaction in the animal kingdom. However, if and how homologous actions are maintained across species is a field of active investigation.

In this Special Issue, we aim to summarize past (reviews) and present (original articles) research on this intriguing pathway and to give the possibility of sharing novel data on the multiple aspects of thyroid hormone signaling in classical as well as emerging animal models.

We invite experts to contribute research papers and critical reviews on TH–TR signaling pathways: from conservation of the sequences to conservation of the function in metazoan organisms, from their role in tissue specification to their role in stem cell maintenance and biology, from their biological importance to their pathological relevance in human diseases.

Dr. Michelina Plateroti
Dr. Maria Sirakov
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • thyroid hormone signaling
  • thyroid hormone nuclear receptors
  • evolution
  • cross-species comparison
  • tissue homeostasis
  • stem cell biology
  • cancer

Published Papers (7 papers)

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Editorial

Jump to: Research, Review

2 pages, 186 KiB  
Editorial
Thyroid Hormone Signaling and Function: News from Classical and Emerging Models
by Maria Sirakov and Michelina Plateroti
Cells 2022, 11(3), 453; https://doi.org/10.3390/cells11030453 - 28 Jan 2022
Cited by 2 | Viewed by 1830
Abstract
According to Brown and Cai, Thyroid hormones (THs) have been considered “the first developmental morphogen ever discovered” [...] Full article
(This article belongs to the Special Issue Thyroid Hormone Signaling and Function: News from Classical and Emerging Models)

Research

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16 pages, 2509 KiB  
Article
Molecular and Cellular Characterization of the TH Pathway in the Sea Urchin Strongylocentrotus purpuratus
by Maria Cocurullo, Periklis Paganos, Natalie J. Wood, Maria I. Arnone and Paola Oliveri
Cells 2023, 12(2), 272; https://doi.org/10.3390/cells12020272 - 10 Jan 2023
Cited by 2 | Viewed by 1723
Abstract
Thyroid Hormones (THs) are a class of signaling molecules produced by coupling iodine with tyrosine residues. In vertebrates, extensive data support their important role in a variety of processes such as metabolism, development and metamorphosis. On the other hand, in invertebrates, the synthesis [...] Read more.
Thyroid Hormones (THs) are a class of signaling molecules produced by coupling iodine with tyrosine residues. In vertebrates, extensive data support their important role in a variety of processes such as metabolism, development and metamorphosis. On the other hand, in invertebrates, the synthesis and role of the THs have been, so far, poorly investigated, thus limiting our understanding of the function and evolution of this important animal signaling pathway. In sea urchins, for example, while several studies focused on the availability and function of external sources of iodotyrosines, preliminary evidence suggests that an endogenous TH pathway might be in place. Here, integrating available literature with an in silico analysis, various homologous genes of the vertebrate TH molecular toolkit have been identified in the sea urchin Strongylocentrotus purpuratus. They include genes involved in the synthesis (Sp-Pxdn), metabolism (Sp-Dios), transport (Sp-Ttrl, Sp-Mct7/8/10) and response (Sp-Thr, Sp-Rxr and Sp-Integrin αP) to thyroid hormones. To understand the cell type(s) involved in TH synthesis and/or response, we studied the spatial expression of the TH toolkit during urchin development. Exploiting single-cell transcriptomics data in conjunction with in situ hybridization and immunohistochemistry, we identified cell types that are potentially producing or responding to THs in the sea urchin. Finally, growing sea urchin embryos until the larva stage with and without a source of inorganic iodine, we provided evidence that iodine organification is important for larval skeleton growth. Full article
(This article belongs to the Special Issue Thyroid Hormone Signaling and Function: News from Classical and Emerging Models)
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13 pages, 2247 KiB  
Article
Evolutionary Adaptation of the Thyroid Hormone Signaling Toolkit in Chordates
by Alfonso Esposito, Luca Ambrosino, Silvano Piazza, Salvatore D’Aniello, Maria Luisa Chiusano and Annamaria Locascio
Cells 2021, 10(12), 3391; https://doi.org/10.3390/cells10123391 - 2 Dec 2021
Cited by 4 | Viewed by 2159
Abstract
The specification of the endostyle in non-vertebrate chordates and of the thyroid gland in vertebrates are fundamental steps in the evolution of the thyroid hormone (TH) signaling to coordinate development and body physiology in response to a range of environmental signals. The physiology [...] Read more.
The specification of the endostyle in non-vertebrate chordates and of the thyroid gland in vertebrates are fundamental steps in the evolution of the thyroid hormone (TH) signaling to coordinate development and body physiology in response to a range of environmental signals. The physiology and biology of TH signaling in vertebrates have been studied in the past, but a complete understanding of such a complex system is still lacking. Non-model species from non-vertebrate chordates may greatly improve our understanding of the evolution of this complex endocrine pathway. Adaptation of already existing proteins in order to perform new roles is a common feature observed during the course of evolution. Through sequence similarity approaches, we investigated the presence of bona fide thyroid peroxidase (TPO), iodothyronine deiodinase (DIO), and thyroid hormone receptors (THRs) in non-vertebrate and vertebrate chordates. Additionally, we determined both the conservation and divergence degrees of functional domains at the protein level. This study supports the hypothesis that non-vertebrate chordates have a functional thyroid hormone signaling system and provides additional information about its possible evolutionary adaptation. Full article
(This article belongs to the Special Issue Thyroid Hormone Signaling and Function: News from Classical and Emerging Models)
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26 pages, 7791 KiB  
Article
Transcriptome and Methylome Analysis Reveal Complex Cross-Talks between Thyroid Hormone and Glucocorticoid Signaling at Xenopus Metamorphosis
by Nicolas Buisine, Alexis Grimaldi, Vincent Jonchere, Muriel Rigolet, Corinne Blugeon, Juliette Hamroune and Laurent M. Sachs
Cells 2021, 10(9), 2375; https://doi.org/10.3390/cells10092375 - 9 Sep 2021
Cited by 10 | Viewed by 2423
Abstract
Background: Most work in endocrinology focus on the action of a single hormone, and very little on the cross-talks between two hormones. Here we characterize the nature of interactions between thyroid hormone and glucocorticoid signaling during Xenopus tropicalis metamorphosis. Methods: We used functional [...] Read more.
Background: Most work in endocrinology focus on the action of a single hormone, and very little on the cross-talks between two hormones. Here we characterize the nature of interactions between thyroid hormone and glucocorticoid signaling during Xenopus tropicalis metamorphosis. Methods: We used functional genomics to derive genome wide profiles of methylated DNA and measured changes of gene expression after hormonal treatments of a highly responsive tissue, tailfin. Clustering classified the data into four types of biological responses, and biological networks were modeled by system biology. Results: We found that gene expression is mostly regulated by either T3 or CORT, or their additive effect when they both regulate the same genes. A small but non-negligible fraction of genes (12%) displayed non-trivial regulations indicative of complex interactions between the signaling pathways. Strikingly, DNA methylation changes display the opposite and are dominated by cross-talks. Conclusion: Cross-talks between thyroid hormones and glucocorticoids are more complex than initially envisioned and are not limited to the simple addition of their individual effects, a statement that can be summarized with the pseudo-equation: TH ∙ GC > TH + GC. DNA methylation changes are highly dynamic and buffered from genome expression. Full article
(This article belongs to the Special Issue Thyroid Hormone Signaling and Function: News from Classical and Emerging Models)
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22 pages, 5947 KiB  
Article
Multi Species Analyses Reveal Testicular T3 Metabolism and Signalling as a Target of Environmental Pesticides
by Valeria Nittoli, Marco Colella, Alfonsina Porciello, Carla Reale, Luca Roberto, Filomena Russo, Nicola A. Russo, Immacalata Porreca, Mario De Felice, Massimo Mallardo and Concetta Ambrosino
Cells 2021, 10(9), 2187; https://doi.org/10.3390/cells10092187 - 25 Aug 2021
Cited by 8 | Viewed by 2841
Abstract
Thyroid hormones (THs) regulate many biological processes in vertebrates, including reproduction. Testicular somatic and germ cells are equipped with the arrays of enzymes (deiodinases), transporters, and receptors necessary to locally maintain the optimal level of THs and their signalling, needed for their functions [...] Read more.
Thyroid hormones (THs) regulate many biological processes in vertebrates, including reproduction. Testicular somatic and germ cells are equipped with the arrays of enzymes (deiodinases), transporters, and receptors necessary to locally maintain the optimal level of THs and their signalling, needed for their functions and spermatogenesis. Pesticides, as chlorpyrifos (CPF) and ethylene thiourea (ETU), impair the function of thyroid and testis, affecting male fertility. However, their ability to disarrange testicular T3 (t-T3) metabolism and signalling is poorly considered. Here, a multi-species analysis involving zebrafish and mouse suggests the damage of t-T3 metabolism and signalling as a mechanism of gonadic toxicity of low-doses CPF and ETU. Indeed, the developmental exposure to both compounds reduces Dio2 transcript in both models, as well as in ex-vivo cultures of murine seminiferous tubules, and it is linked to alteration of steroidogenesis and germ cell differentiation. A major impact on spermatogonia was confirmed molecularly by the expression of their markers and morphologically evidenced in zebrafish. The results reveal that in the adopted models, exposure to both pesticides alters the t-T3 metabolism and signalling, affecting the reproductive capability. Our data, together with previous reports suggest zebrafish as an evaluable model in assessing the action of compounds impairing locally T3 signalling. Full article
(This article belongs to the Special Issue Thyroid Hormone Signaling and Function: News from Classical and Emerging Models)
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23 pages, 4363 KiB  
Article
Thyroid Hormone Receptor Is Essential for Larval Epithelial Apoptosis and Adult Epithelial Stem Cell Development but Not Adult Intestinal Morphogenesis during Xenopus tropicalis Metamorphosis
by Yuki Shibata, Yuta Tanizaki, Hongen Zhang, Hangnoh Lee, Mary Dasso and Yun-Bo Shi
Cells 2021, 10(3), 536; https://doi.org/10.3390/cells10030536 - 3 Mar 2021
Cited by 19 | Viewed by 2996
Abstract
Vertebrate postembryonic development is regulated by thyroid hormone (T3). Of particular interest is anuran metamorphosis, which offers several unique advantages for studying the role of T3 and its two nuclear receptor genes, TRα and TRβ, during postembryonic development. We have recently [...] Read more.
Vertebrate postembryonic development is regulated by thyroid hormone (T3). Of particular interest is anuran metamorphosis, which offers several unique advantages for studying the role of T3 and its two nuclear receptor genes, TRα and TRβ, during postembryonic development. We have recently generated TR double knockout (TRDKO) Xenopus tropicalis animals and reported that TR is essential for the completion of metamorphosis. Furthermore, TRDKO tadpoles are stalled at the climax of metamorphosis before eventual death. Here we show that TRDKO intestine lacked larval epithelial cell death and adult stem cell formation/proliferation during natural metamorphosis. Interestingly, TRDKO tadpole intestine had premature formation of adult-like epithelial folds and muscle development. In addition, T3 treatment of premetamorphic TRDKO tadpoles failed to induce any metamorphic changes in the intestine. Furthermore, RNA-seq analysis revealed that TRDKO altered the expression of many genes in biological pathways such as Wnt signaling and the cell cycle that likely underlay the inhibition of larval epithelial cell death and adult stem cell development caused by removing both TR genes. Our data suggest that liganded TR is required for larval epithelial cell degeneration and adult stem cell formation, whereas unliganded TR prevents precocious adult tissue morphogenesis such as smooth-muscle development and epithelial folding. Full article
(This article belongs to the Special Issue Thyroid Hormone Signaling and Function: News from Classical and Emerging Models)
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Review

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19 pages, 2011 KiB  
Review
Central vs. Peripheral Action of Thyroid Hormone in Adaptive Thermogenesis: A Burning Topic
by Yanis Zekri, Frédéric Flamant and Karine Gauthier
Cells 2021, 10(6), 1327; https://doi.org/10.3390/cells10061327 - 27 May 2021
Cited by 14 | Viewed by 5922
Abstract
Thyroid hormones (TH) contribute to the control of adaptive thermogenesis, which is associated with both higher energy expenditure and lower body mass index. While it was clearly established that TH act directly in the target tissues to fulfill its metabolic activities, some studies [...] Read more.
Thyroid hormones (TH) contribute to the control of adaptive thermogenesis, which is associated with both higher energy expenditure and lower body mass index. While it was clearly established that TH act directly in the target tissues to fulfill its metabolic activities, some studies have rather suggested that TH act in the hypothalamus to control these processes. This paradigm shift has subjected the topic to intense debates. This review aims to recapitulate how TH control adaptive thermogenesis and to what extent the brain is involved in this process. This is of crucial importance for the design of new pharmacological agents that would take advantage of the TH metabolic properties. Full article
(This article belongs to the Special Issue Thyroid Hormone Signaling and Function: News from Classical and Emerging Models)
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