Evolutionary Adaptation of the Thyroid Hormone Signaling Toolkit in Chordates

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.

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Role of the type 2 iodothyronine deiodinase (D2) in the control of thyroid hormone signaling

Biochimica et Biophysica Acta (BBA) - General Subjects ◽

10.1016/j.bbagen.2012.08.019 ◽

2013 ◽

Vol 1830 (7) ◽

pp. 3956-3964 ◽

Cited By ~ 80

Author(s):

Rafael Arrojo e Drigo ◽

Tatiana L. Fonseca ◽

Joao Pedro Saar Werneck-de-Castro ◽

Antonio C. Bianco

Keyword(s):

Thyroid Hormone ◽

Hormone Signaling ◽

Iodothyronine Deiodinase

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Estrogen and Thyroid Hormone Receptor Interactions: Physiological Flexibility by Molecular Specificity

Physiological Reviews ◽

10.1152/physrev.00014.2002 ◽

2002 ◽

Vol 82 (4) ◽

pp. 923-944 ◽

Cited By ~ 67

Author(s):

Nandini Vasudevan ◽

Sonoko Ogawa ◽

Donald Pfaff

Keyword(s):

Thyroid Hormone ◽

Hormone Receptors ◽

Thyroid Hormone Receptor ◽

Hormone Signaling ◽

Cell Type ◽

Reproductive Behaviors ◽

Receptor Interactions ◽

Molecular Specificity

The influence of thyroid hormone on estrogen actions has been demonstrated both in vivo and in vitro. In transient transfection assays, the effects of liganded thyroid hormone receptors (TR) on transcriptional facilitation by estrogens bound to estrogen receptors (ER) display specificity according to the following: 1) ER isoform, 2) TR isoform, 3) the promoter through which transcriptional facilitation occurs, and 4) cell type. Some of these molecular phenomena may be related to thyroid hormone signaling of seasonal limitations upon reproduction. The various combinations of these molecular interactions provide multiple and flexible opportunities for relations between two major hormonal systems important for neuroendocrine feedbacks and reproductive behaviors.

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Thyroid hormone receptor localization in target tissues

Journal of Endocrinology ◽

10.1530/joe-17-0708 ◽

2018 ◽

Vol 237 (1) ◽

pp. R19-R34 ◽

Cited By ~ 20

Author(s):

Cyril S Anyetei-Anum ◽

Vincent R Roggero ◽

Lizabeth A Allison

Keyword(s):

Thyroid Hormone ◽

Nuclear Export ◽

Cellular Response ◽

Hormone Receptors ◽

Target Genes ◽

Thyroid Hormone Receptor ◽

Hormone Signaling ◽

Transport Pathways ◽

Nuclear Localization Signals ◽

Specific Localization

The thyroid hormone receptors, TRα1, TRβ1 and other subtypes, are members of the nuclear receptor superfamily that mediate the action of thyroid hormone signaling in numerous tissues to regulate important physiological and developmental processes. Their most well-characterized role is as ligand-dependent transcription factors; TRs bind thyroid hormone response elements in the presence or absence of thyroid hormone to facilitate the expression of target genes. Although primarily residing in the nucleus, TRα1 and TRβ1 shuttle rapidly between the nucleus and cytoplasm. We have identified multiple nuclear localization signals and nuclear export signals within TRα1 and TRβ1 that interact with importins and exportins, respectively, to mediate translocation across the nuclear envelope. More recently, enigmatic cytoplasmic functions have been ascribed to other TR subtypes, expanding the diversity of the cellular response to thyroid hormone. By integrating data on localization signal motifs, this review provides an overview of the complex interplay between TR’s dynamic transport pathways and thyroid hormone signaling activities. We examine the variation in TR subtype response to thyroid hormone signaling, and what is currently known about regulation of the variety of tissue-specific localization patterns, including targeting to the nucleus, the mitochondria and the inner surface of the plasma membrane.

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