The Role of Thyroid Hormone Signaling in the Prevention of Digestive System Cancers

Abstract. Basal plasma levels for adrenalin (A), noradrenalin (NA), l-triiodothyronine (T3), and l-thyroxine (T4) were determined in rats with a chronically inserted catheter. The experiments described in this report were started 3 days after the surgical procedure when T3 and T4 levels had returned to normal. Basal levels for the catecholamines were reached already 4 h after the operation. The T3/T4 ratio in plasma was significantly increased after 3, 7, and 14 days in rats kept at 4°C and the same holds for the iodide in the 24-h urine after 7 and 14 days at 4°C. The venous NA plasma concentration was increased 6- to 12-fold during the same period of exposure to cold, whereas the A concentration remained at the basal level. During infusion of NA at 23°C the T3/T4 ratio in plasma was significantly increased after 7 days compared to pair-fed controls, and the same holds for the iodide excretion in the 24-h urine. This paper presents further evidence for a role of the sympathetic nervous system on T4 metabolism in rats at resting conditions.

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Biological activity of novel thyroid hormone analogues: role of Na+ taurocholate cotransporting polypeptide in liver selectivity

Endocrine Abstracts ◽

10.1530/endoabs.37.oc6.2 ◽

2015 ◽

Author(s):

Giulia Brigante ◽

Bo Carlsson ◽

Simone Kersseboom ◽

Robin P Peeters ◽

Theo J Visser

Keyword(s):

Biological Activity ◽

Thyroid Hormone

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Pan-cancer analysis of thyroid hormone signaling pathway reveals new possible targets for combinations therapy

Endocrine Abstracts ◽

10.1530/endoabs.63.p666 ◽

2019 ◽

Author(s):

Karolina Hanusek ◽

Piotr Popławski ◽

Agnieszka Piekiełko-Witkowska

Keyword(s):

Thyroid Hormone ◽

Signaling Pathway ◽

Hormone Signaling ◽

Pan Cancer

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MiRNA-145 and Its Direct Downstream Targets in Digestive System Cancers: A Promising Therapeutic Target

Current Pharmaceutical Design ◽

10.2174/1381612826666201029095702 ◽

2020 ◽

Vol 26 ◽

Author(s):

Yini Ma ◽

Xiu Cao ◽

Guojuan Shi ◽

Tianlu Shi

Keyword(s):

Digestive System ◽

Target Genes ◽

Malignant Neoplasm ◽

Vital Role ◽

Diagnostic Biomarkers ◽

Cellular Processes ◽

Promising Therapeutic Target ◽

Direct Target ◽

Potential Strategy

: MicroRNAs (miRNAs) play a vital role in the onset and development of many diseases, including cancers. Emerging evidence shows that numerous miRNAs have the potential to be used as diagnostic biomarkers for cancers, and miRNA-based therapy may be a promising therapy for the treatment of malignant neoplasm. MicroRNA-145 (miR-145) has been considered to play certain roles in various cellular processes, such as proliferation, differentiation and apoptosis, via modulating expression of direct target genes. Recent reports show that miR-145 participates in the progression of digestive system cancers, and plays crucial and novel roles for cancer treatment. In this review, we summarize the recent knowledge concerning the function of miR-145 and its direct targets in digestive system cancers. We discuss the potential role of miR-145 as valuable biomarkers for digestive system cancers and how miR-145 regulates these digestive system cancers via different targets to explore the potential strategy of targeting miR-145.

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Minireview: Thyroid Hormone Transporters: The Knowns and the Unknowns

Molecular Endocrinology ◽

10.1210/me.2010-0095 ◽

2011 ◽

Vol 25 (1) ◽

pp. 1-14 ◽

Cited By ~ 256

Author(s):

W. Edward Visser ◽

Edith C. H. Friesema ◽

Theo J. Visser

Keyword(s):

Thyroid Hormone ◽

Organic Anion ◽

Psychomotor Retardation ◽

Cellular Level ◽

Monocarboxylate Transporter ◽

Causative Role ◽

Organic Anion Transporting Polypeptide ◽

Neurological Abnormalities ◽

Knockout Animals

The effects of thyroid hormone (TH) on development and metabolism are exerted at the cellular level. Metabolism and action of TH take place intracellularly, which require transport of the hormone across the plasma membrane. This process is mediated by TH transporter proteins. Many TH transporters have been identified at the molecular level, although a few are classified as specific TH transporters, including monocarboxylate transporter (MCT)8, MCT10, and organic anion-transporting polypeptide 1C1. The importance of TH transporters for physiology has been illustrated dramatically by the causative role of MCT8 mutations in males with psychomotor retardation and abnormal serum TH concentrations. Although Mct8 knockout animals have provided insight in the mechanisms underlying parts of the endocrine phenotype, they lack obvious neurological abnormalities. Thus, the pathogenesis of the neurological abnormalities in males with MCT8 mutations is not fully understood. The prospects of identifying other transporters and transporter-based syndromes promise an exciting future in the TH transporter field.

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The Role of Thyroid Hormone in Neuronal Protection

Comprehensive Physiology ◽

10.1002/cphy.c200019 ◽

2021 ◽

pp. 1-21

Author(s):

Yan‐Yun Liu ◽

Gregory A. Brent

Keyword(s):

Thyroid Hormone ◽

Neuronal Protection

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p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) modulates co-operation between myocyte enhancer factor 2A (MEF2A) and thyroid hormone receptor-retinoid X receptor

Biochemical Journal ◽

10.1042/bj20020057 ◽

2003 ◽

Vol 369 (3) ◽

pp. 477-484 ◽

Cited By ~ 24

Author(s):

Antonio De LUCA ◽

Anna SEVERINO ◽

Paola De PAOLIS ◽

Giuliano COTTONE ◽

Luca De LUCA ◽

...

Keyword(s):

Thyroid Hormone ◽

Binding Protein ◽

Camp Response Element Binding ◽

Creb Binding Protein ◽

Camp Response Element ◽

Response Element ◽

Adenovirus E1a ◽

Element Binding Protein ◽

Enhancer Factor

Thyroid hormone receptors (TRs) and members of the myocyte enhancer factor 2 (MEF2) family are involved in the regulation of muscle-specific gene expression during myogenesis. Physical interaction between these two factors is required to synergistically activate gene transcription. p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) interacting with transcription factors is able to increase their activity on target gene promoters. We investigated the role of p300 in regulating the TR—MEF2A complex. To this end, we mapped the regions of these proteins involved in physical interactions and we evaluated the expression of a chloramphenicol acetyltransferase (CAT) reporter gene in U2OS cells under control of the α-myosin heavy chain promoter containing the thyroid hormone response element (TRE). Our results suggested a role of p300/CBP in mediating the transactivation effects of the TR—retenoid X receptor (RxR)—MEF2A complex. Our findings showed that the same C-terminal portion of p300 binds the N-terminal domains of both TR and MEF2A, and our in vivo studies demonstrated that TR, MEF2A and p300 form a ternary complex. Moreover, by the use of CAT assays, we demonstrated that adenovirus E1A inhibits activation of transcription by TR—RxR—MEF2A—p300 but not by TR—RxR—MEF2A. Our data suggested that p300 can bind and modulate the activity of TR—RxR—MEF2A at TRE. In addition, it is speculated that p300 might modulate the activity of the TR—RxR—MEF2A complex by recruiting a hypothetical endogenous inhibitor which may act like adenovirus E1A.

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