Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Thyroid Hormone and Thyroid Hormone-Related Compounds: Molecular Pathways and Effects

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 17560

Share This Special Issue

Special Issue Editors

Prof. Dr. Laura Raimondi

E-Mail Website
Guest Editor

Department of Neuroscience, Psychology, Drug Sciences and Child Health, University of Firenze, 50139 Firenze, Italy
Interests: thyroid hormone metabolites; endopharmacology; diabetes; histamine
Special Issues, Collections and Topics in MDPI journals

Dr. Elisa Landucci

E-Mail
Guest Editor

Department of Health Sciences, University of Florence, Florence, Italy

Dr. Annunziatina Laurino

E-Mail Website
Guest Editor

Department of Molecular and Developmental Medicine, Molecular Medicine Section, University of Siena, 53100 Siena, Italy
Interests: thyroid; neuroscience; skeletal muscle
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Homeostatic thyroid secretion is one of the conditions required to maintain healthy and functional thyroid hormone (TH) target tissues. TH exerts control on the growth, metabolism, differentiation, and survival of most mammalian cells. Thyroid diseases are risk factors for aberrant cell functions and a pathogenic ground for several chronic and degenerative diseases. TH-related effects derive from the activation of pathways dependent or independent of TH receptors activation.

Recent evidence suggests TH metabolism may generate compounds endowed with biological activities. These compounds belong to three families, i.e., tyronines, thyronamines, and thyroacetic or thyropropionic acids, and occur endogenously, potentially produced in thyroid target tissues and possibly participating in TH effects, though their physio-pathological meaning is not clear.

The aim of this Special Issue is to collect articles and reviews describing the biochemical and molecular aspects of TH, the physio-pharmacological activities of TH metabolites, and the relationship between TH and TH metabolites in healthy and pathological conditions.

Prof. Dr. Laura Raimondi
Dr. Elisa Landucci
Dr. Annunziatina Laurino
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

cell signaling
hormone metabolism
neuromodulation
degenerative diseases
hormone targets

Published Papers (7 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Editorial

Jump to: Research

3 pages, 169 KiB

Open AccessEditorial

Thyroid Homeostasis: An Intricate Network of Production, Transport, Metabolism and Receptors Interaction

by Annunziatina Laurino and Laura Raimondi

Int. J. Mol. Sci. 2022, 23(12), 6751; https://doi.org/10.3390/ijms23126751 - 17 Jun 2022

Cited by 3 | Viewed by 1015

Abstract

Correct thyroid function is regarded essential for maintaining the growth, differentiation and survival of most mammalian cells at homeostatic conditions [...] Full article

(This article belongs to the Special Issue Thyroid Hormone and Thyroid Hormone-Related Compounds: Molecular Pathways and Effects)

Research

Jump to: Editorial

13 pages, 3301 KiB

Open AccessArticle

Redox Properties of 3-Iodothyronamine (T1AM) and 3-Iodothyroacetic Acid (TA1)

by Manuela Gencarelli, Maura Lodovici, Lorenza Bellusci, Laura Raimondi and Annunziatina Laurino

Int. J. Mol. Sci. 2022, 23(5), 2718; https://doi.org/10.3390/ijms23052718 - 28 Feb 2022

Cited by 2 | Viewed by 1986

Abstract

3-iodothyronamine (T1AM) and 3-iodothyroacetic acid (TA1) are thyroid-hormone-related compounds endowed with pharmacological activity through mechanisms that remain elusive. Some evidence suggests that they may have redox features. We assessed the chemical activity of T1AM and TA1 at pro-oxidant conditions. Further, in the cell model consisting of brown adipocytes (BAs) differentiated for 6 days in the absence (M cells) or in the presence of 20 nM T1AM (M + T1AM cells), characterized by pro-oxidant metabolism, or TA1 (M + TA1 cells), we investigated the expression/activity levels of pro- and anti-oxidant proteins, including UCP-1, sirtuin-1 (SIRT1), mitochondrial monoamine (MAO-A and MAO-B), semicarbazide-sensitive amine oxidase (SSAO), and reactive oxygen species (ROS)-dependent lipoperoxidation. T1AM and TA1 showed in-vitro antioxidant and superoxide scavenging properties, while only TA1 acted as a hydroxyl radical scavenger. M + T1AM cells showed higher lipoperoxidation levels and reduced SIRT1 expression and activity, similar MAO-A, but higher MAO-B activity in terms of M cells. Instead, the M + TA1 cells exhibited increased levels of SIRT1 protein and activity and significantly lower UCP-1, MAO-A, MAO-B, and SSAO in comparison with the M cells, and did not show signs of lipoperoxidation. Our results suggest that SIRT1 is the mediator of T1AM and TA1 pro-or anti-oxidant effects as a result of ROS intracellular levels, including the hydroxyl radical. Here, we provide evidence indicating that T1AM and TA1 administration impacts on the redox status of a biological system, a feature that indicates the novel mechanism of action of these two thyroid-hormone-related compounds. Full article

(This article belongs to the Special Issue Thyroid Hormone and Thyroid Hormone-Related Compounds: Molecular Pathways and Effects)

► Show Figures

Figure 1

10 pages, 2805 KiB

Open AccessArticle

Subcellular Distribution of Thyroid Hormone Receptor Beta in Ovarian Cancer

by Sabine Heublein, Udo Jeschke, Cornelia Sattler, Christina Kuhn, Anna Hester, Bastian Czogalla, Fabian Trillsch, Sven Mahner, Doris Mayr, Elisa Schmoeckel and Nina Ditsch

Int. J. Mol. Sci. 2022, 23(5), 2698; https://doi.org/10.3390/ijms23052698 - 28 Feb 2022

Cited by 3 | Viewed by 1542

Abstract

Background: Since the most well-known function of thyroid hormone receptors (TRs) relies on their ability to act as ligand-activated transcription factors, their subcellular localization has been recognized to be relevant for their biological meaning. The current study aimed to determine the prevalence and subcellular distribution of TR beta and TR beta-1 in ovarian cancer (OC). Methods: Tissue was collected from 153 patients that had undergone surgery due to OC at the Department of Obstetrics and Gynaecology of the Ludwig-Maximilians-University Munich. Immunohistochemistry detecting TR beta and TR beta-1 was performed. Staining signals were quantified and tested for association with clinico-pathological parameters including overall survival (OS). Results: The subcellular distribution of TR beta and TR beta-1 differed among histologic subtypes, grade and FIGO stage. TR beta positivity was strongly linked to shortened overall survival (p < 0.001). Strikingly, this shortened OS was mainly attributed to those cases showing complete (p = 0.005) or incomplete shift of TR beta to the cytoplasm (p < 0.001). Significance was lost in multivariate testing. Conclusions: Cytoplasmatic localization of TR beta was associated with reduced OS, at least in univariate analysis. Since TRs have long been supposed to mainly function via the regulation of gene transcription in the nucleus, cytoplasmatic shifting might be interpreted as a regulator of their activity. Full article

(This article belongs to the Special Issue Thyroid Hormone and Thyroid Hormone-Related Compounds: Molecular Pathways and Effects)

► Show Figures

Figure 1

19 pages, 1220 KiB

Open AccessArticle

A New Mechanism in THRA Resistance: The First Disease-Associated Variant Leading to an Increased Inhibitory Function of THRA2

by Sarah Paisdzior, Ellen Knierim, Gunnar Kleinau, Heike Biebermann, Heiko Krude, Rachel Straussberg and Markus Schuelke

Int. J. Mol. Sci. 2021, 22(10), 5338; https://doi.org/10.3390/ijms22105338 - 19 May 2021

Cited by 8 | Viewed by 2590

Abstract

The nuclear thyroid hormone receptors (THRs) are key mediators of thyroid hormone function on the cellular level via modulation of gene expression. Two different genes encode THRs (THRA and THRB), and are pleiotropically involved in development, metabolism, and growth. The THRA1 and THRA2 isoforms, which result from alternative splicing of THRA, differ in their C-terminal ligand-binding domain (LBD). Most published disease-associated THRA variants are located in the LBD of THRA1 and impede triiodothyronine (T3) binding. This keeps the nuclear receptor in an inactive state and inhibits target gene expression. Here, we investigated a new dominant THRA variant (chr17:g.38,241,010A > G, GRCh37.13 | c.518A > G, NM_199334 | p.(E173G), NP_955366), which is located between the DNA- and ligand-binding domains and affects both splicing isoforms. Patients presented partially with hypothyroid (intellectual disability, motor developmental delay, brain atrophy, and constipation) and partially with hyperthyroid symptoms (tachycardia and behavioral abnormalities) to varying degrees. Functional characterization of THRA1p.(E173G) by reporter gene assays revealed increased transcriptional activity in contrast to THRA1(WT), unexpectedly revealing the first gain-of-function mutation found in THRA1. The THRA2 isoform does not bind T3 and antagonizes THRA1 action. Introduction of p.(E173G) into THRA2 increased its inhibitory effect on THRA1, which helps to explain the hypothyroid symptoms seen in our patients. We used protein structure models to investigate possible underlying pathomechanisms of this variant with a gain-of-antagonistic function and suggest that the p.(E173G) variant may have an influence on the dimerization domain of the nuclear receptor. Full article

(This article belongs to the Special Issue Thyroid Hormone and Thyroid Hormone-Related Compounds: Molecular Pathways and Effects)

► Show Figures

Figure 1

17 pages, 1982 KiB

Open AccessArticle

A Blunted Sympathetic Function and an Enhanced Nitrergic Activity Contribute to Reduce Mesenteric Resistance in Hyperthyroidism

by Laia Cros-Brunsó, Laura Camacho-Rodríguez, Ángel Martínez-González, Pablo Llévenes, Mercedes Salaices, Ana Belen García-Redondo and Javier Blanco-Rivero

Int. J. Mol. Sci. 2021, 22(2), 570; https://doi.org/10.3390/ijms22020570 - 08 Jan 2021

Cited by 3 | Viewed by 2124

Abstract

We aimed to determine whether an experimental model of hyperthyroidism could alter the function of sympathetic and nitrergic components of mesenteric innervation. For this purpose, male Wistar rats were divided into (1) control rats (CT) and (2) rats infused with L-Thyroxine (HT). Body weight gain and adipose tissue accumulation were lower in HT rats, while systolic blood pressure and citrate synthase activity in the soleus muscle were increased by HT. In segments from the superior mesenteric artery, the application of an electrical field stimulation (EFS) induced a vasoconstrictor response, which was lower in arteries from HT animals. The alpha-adrenoceptor antagonist phentolamine diminished EFS-induced vasoconstriction to a lower extent in HT arteries, while the purinergic receptor antagonist suramin reduced contractile response to EFS only in segments from CT. In line with this, noradrenaline release, tyrosine hydroxylase expression and activation and dopamine β hydroxylase expression were diminished in HT. The unspecific nitric oxide synthase (NOS) inhibitor L-NAME increased EFS-induced vasoconstriction more markedly in segments from HT rats. NO release was enhanced in HT, probably due to an enhancement in neuronal NOS activity, in which a hyperactivation of both PKC and PI3K-AKT signaling pathways might play a relevant role. In conclusion, perivascular mesenteric innervation might contribute to reduce the vascular resistance observed in hyperthyroidism. Full article

(This article belongs to the Special Issue Thyroid Hormone and Thyroid Hormone-Related Compounds: Molecular Pathways and Effects)

► Show Figures

Figure 1

34 pages, 8154 KiB

Open AccessArticle

The Thyroid Hormone Transporter Mct8 Restricts Cathepsin-Mediated Thyroglobulin Processing in Male Mice through Thyroid Auto-Regulatory Mechanisms That Encompass Autophagy

by Vaishnavi Venugopalan, Alaa Al-Hashimi, Maren Rehders, Janine Golchert, Vivien Reinecke, Georg Homuth, Uwe Völker, Mythili Manirajah, Adam Touzani, Jonas Weber, Matthew S. Bogyo, Francois Verrey, Eva K. Wirth, Ulrich Schweizer, Heike Heuer, Janine Kirstein and Klaudia Brix

Int. J. Mol. Sci. 2021, 22(1), 462; https://doi.org/10.3390/ijms22010462 - 05 Jan 2021

Cited by 7 | Viewed by 4106

Abstract

The thyroid gland is both a thyroid hormone (TH) generating as well as a TH responsive organ. It is hence crucial that cathepsin-mediated proteolytic cleavage of the precursor thyroglobulin is regulated and integrated with the subsequent export of TH into the blood circulation, which is enabled by TH transporters such as monocarboxylate transporters Mct8 and Mct10. Previously, we showed that cathepsin K-deficient mice exhibit the phenomenon of functional compensation through cathepsin L upregulation, which is independent of the canonical hypothalamus-pituitary-thyroid axis, thus, due to auto-regulation. Since these animals also feature enhanced Mct8 expression, we aimed to understand if TH transporters are part of the thyroid auto-regulatory mechanisms. Therefore, we analyzed phenotypic differences in thyroid function arising from combined cathepsin K and TH transporter deficiencies, i.e., in Ctsk^-/-/Mct10^-/-, Ctsk^-/-/Mct8^-/y, and Ctsk^-/-/Mct8^-/y/Mct10^-/-. Despite the impaired TH export, thyroglobulin degradation was enhanced in the mice lacking Mct8, particularly in the triple-deficient genotype, due to increased cathepsin amounts and enhanced cysteine peptidase activities, leading to ongoing thyroglobulin proteolysis for TH liberation, eventually causing self-thyrotoxic thyroid states. The increased cathepsin amounts were a consequence of autophagy-mediated lysosomal biogenesis that is possibly triggered due to the stress accompanying intrathyroidal TH accumulation, in particular in the Ctsk^-/-/Mct8^-/y/Mct10^-/- animals. Collectively, our data points to the notion that the absence of cathepsin K and Mct8 leads to excessive thyroglobulin degradation and TH liberation in a non-classical pathway of thyroid auto-regulation. Full article

(This article belongs to the Special Issue Thyroid Hormone and Thyroid Hormone-Related Compounds: Molecular Pathways and Effects)

► Show Figures

Graphical abstract

16 pages, 2834 KiB

Open AccessArticle

Thyroid Hormone Signaling in Embryonic Stem Cells: Crosstalk with the Retinoic Acid Pathway

by Mercedes Fernández, Micaela Pannella, Vito Antonio Baldassarro, Alessandra Flagelli, Giuseppe Alastra, Luciana Giardino and Laura Calzà

Int. J. Mol. Sci. 2020, 21(23), 8945; https://doi.org/10.3390/ijms21238945 - 25 Nov 2020

Cited by 7 | Viewed by 3030

Abstract

While the role of thyroid hormones (THs) during fetal and postnatal life is well-established, their role at preimplantation and during blastocyst development remains unclear. In this study, we used an embryonic stem cell line isolated from rat (RESC) to study the effects of THs and retinoic acid (RA) on early embryonic development during the pre-implantation stage. The results showed that THs play an important role in the differentiation/maturation processes of cells obtained from embryoid bodies (EB), with thyroid hormone nuclear receptors (TR) (TRα and TRβ), metabolic enzymes (deiodinases 1, 2, 3) and membrane transporters (Monocarboxylate transporters -MCT- 8 and 10) being expressed throughout in vitro differentiation until the Embryoid body (EB) stage. Moreover, thyroid hormone receptor antagonist TR (1-850) impaired RA-induced neuroectodermal lineage specification. This effect was significantly higher when cells were treated with retinoic acid (RA) to induce neuroectodermal lineage, studied through the gene and protein expression of nestin, an undifferentiated progenitor marker from the neuroectoderm lineage, as established by nestin mRNA and protein regulation. These results demonstrate the contribution of the two nuclear receptors, TR and RA, to the process of neuroectoderm maturation of the in vitro model embryonic stem cells obtained from rat. Full article

(This article belongs to the Special Issue Thyroid Hormone and Thyroid Hormone-Related Compounds: Molecular Pathways and Effects)

► Show Figures

Journal Menu

Journal Browser

Thyroid Hormone and Thyroid Hormone-Related Compounds: Molecular Pathways and Effects

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (7 papers)

Editorial

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI