Thyroid Hormone Transporters

Endocrine Reviews, Год журнала: 2019, Номер 41(2), С. 146 - 201

Опубликована: Ноя. 22, 2019

Abstract Thyroid hormone transporters at the plasma membrane govern intracellular bioavailability of thyroid hormone. Monocarboxylate transporter (MCT) 8 and MCT10, organic anion transporting polypeptide (OATP) 1C1, SLC17A4 are currently known as displaying highest specificity toward hormones. Structure-function studies using homology modeling mutational screens have led to better understanding molecular basis transport. Mutations in MCT8 OATP1C1 been associated with clinical disorders. Different animal models provided insight into functional role transporters, particular MCT8. treatment strategies for deficiency explored, which analogue therapy is applied patients. Future may reveal identity as-yet-undiscovered transporters. Complementary employing human will provide further health disease.

Язык: Английский

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The role of thyroid hormone in metabolism and metabolic syndrome

Therapeutic Advances in Endocrinology and Metabolism, Год журнала: 2020, Номер 11

Опубликована: Янв. 1, 2020

Metabolic syndrome (MetS) and thyroid dysfunction are common in clinical practice. The objectives of this review to discuss some proposed mechanisms by which dysfunctions may lead MetS, describe the bidirectional relationship between hormones (THs) adiposity finally, resume a list recent studies humans that evaluated possible associations hormone status MetS or its components. Not solely THs, but also metabolites regulate metabolic rate, influencing adiposity. enrolled related direct effect on adenosine triphosphate (ATP) utilization, uncoupling synthesis ATP, mitochondrial biogenesis, inotropic chronotropic effects. THs act controlling core body temperature, appetite, sympathetic activity. In way, function is affected Leptin one hallmarks, pro-inflammatory cytokines insulin resistance impact perhaps structure. development weight gain have been positively associated with thyroid-stimulating (TSH) several studies. Adverse glucose metabolism be hyperthyroidism, reduction higher serum TSH, as do abnormal triglyceride levels. Hypo- hyperthyroidism blood pressure (BP), consequence genomic nongenomic action vasculature heart. summary, interaction components complex not fully understood. More longitudinal each all confounding variables interact endpoints exposure factors still necessary.

Язык: Английский

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Primary hypothyroidism and quality of life

Nature Reviews Endocrinology, Год журнала: 2022, Номер 18(4), С. 230 - 242

Опубликована: Янв. 18, 2022

Язык: Английский

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Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions

Endocrinology and Metabolism, Год журнала: 2021, Номер 36(5), С. 952 - 964

Опубликована: Окт. 22, 2021

Thyroid hormone (TH) signaling is strictly regulated by iodothyronine deiodinase activity, which both preserves the circulating levels of biologically active triiodothyronine (T3) and regulates TH homeostasis at local level, in a cell- time-dependent manner. Three deiodinases have been identified—namely 1 (DIO1), DIO2, DIO3—that differ their catalytic properties tissue distribution. The represent dynamic system that changes different stages life according to functions roles various cell types tissues. Deiodinase activity level permits cell-targeted fine regulation homeostasis, mediating activation (DIO1 DIO2) inactivation (DIO3) THs. driving force leads T3-target cells towards customized signaling, takes into account hormonal tissue-specific response. This review analyzes complex role physiological pathological contexts, exploring new challenges opportunities deriving from deeper knowledge dynamics underlying functions.

Язык: Английский

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Genomic and Non-Genomic Mechanisms of Action of Thyroid Hormones and Their Catabolite 3,5-Diiodo-L-Thyronine in Mammals

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(11), С. 4140 - 4140

Опубликована: Июнь 10, 2020

Since the realization that cellular homologs of a gene found in retrovirus contributes to erythroblastosis birds (v-erbA), i.e. proto-oncogene c-erbA encodes nuclear receptors for thyroid hormones (THs), most interest THs focalized on their ability control transcription. It was found, indeed, that, by regulating expression many tissues, these could mediate critical events both development and adult organisms. Among effects, much attention given increase energy expenditure, they were early proposed as anti-obesity drugs. However, clinical use has been strongly challenged concomitant onset toxic especially heart. Notably, it clearly demonstrated besides direct action transcription (genomic effects), also have non-genomic mediated cell membrane and/or mitochondrial binding sites, sometimes triggered endogenous catabolites. latter molecules, 3,5-diiodo-L-thyronine (3,5-T2) attracting increasing because some its metabolic effects are similar those induced T3, but seems be safer. The main target 3,5-T2 appears mitochondria, hypothesized acting mainly function oxidative stress, might prevent revert tissue damages hepatic steatosis hyper-lipid diet, while concomitantly reducing circulating levels low density lipoproteins (LDL) triglycerides. Besides summary concerning general metabolism THs, well genomic herein we will discuss resistance possible mechanisms 3,5-T2, relation drug.

Язык: Английский

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Deiodinases control local cellular and systemic thyroid hormone availability

Free Radical Biology and Medicine, Год журнала: 2022, Номер 193, С. 59 - 79

Опубликована: Окт. 4, 2022

Iodothyronine deiodinases (DIO) are a family of selenoproteins controlling systemic and local availability the major thyroid hormone l-thyroxine (T4), prohormone secreted by gland. T4 is activated to active 3,3'-5-triiodothyronine (T3) two 5'-deiodinases, DIO1 DIO2. DIO3, 5-deiodinase selenoenzyme inactivates both its form T3. DIOs show species-specific different patterns temporo-spatial expression, regulation function exhibit mechanisms reaction inhibitor sensitivities. The main regulators DIO expression status, several growth factors, cytokines altered pathophysiological conditions. Selenium (Se) status has modest impact on translation. rank high in priority selenium supply various selenoproteins; thus, their impaired only during severe deficiency. variants, polymorphisms, SNPs rare mutations have been identified. Development isozyme selective drugs ongoing. A first X-ray structure reported for DIO3. This review focusses biochemical characteristics mechanisms, relationships between importance provision Nutritional, pharmacological, environmental factors inhibitors, such as endocrine disruptors, functions.

Язык: Английский

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Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism

The Journal of Clinical Endocrinology & Metabolism, Год журнала: 2021, Номер 106(11), С. e4400 - e4413

Опубликована: Июнь 29, 2021

Abstract Introduction Studies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated thyroid extract (DTE) did not detect consistent superiority of either treatment. Here, we investigated these therapies, focusing on the whole group LT4-treated hypothyroid patients, while also exploring most symptomatic patients. Methodology Prospective, randomized, double-blind, crossover study 75 patients randomly allocated to 1 3 treatment arms, LT4, LT3, and DTE, for 22 weeks. The primary outcomes were posttreatment scores 36-point symptom questionnaire (TSQ-36), 12-point quality life general health (GHQ-12), Wechsler memory scale-version IV (VMS-IV), Beck Depression Inventory (BDI). Secondary endpoints included preference, biochemical metabolic parameters, etiology hypothyroidism, Thr92Ala-DIO2 gene polymorphism. Analyses performed a linear mixed model using subject as random factor fixed effect. Results Serum TSH remained within reference range across all arms. There no differences secondary outcomes, except minor increase in heart rate caused by DTE. Treatment preference was different there interferences hypothyroidism polymorphism outcomes. Subgroup analyses 1/3 revealed strong containing T3, which improved performance TSQ-36, GHQ-12, BDI, visual index (VMS-IV component). Conclusions As group, similar among taking DTE vs T3 LT4. However, those that preferred responded positively LT3

Язык: Английский

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The interplay of thyroid hormones and the immune system – where we stand and why we need to know about it

European Journal of Endocrinology, Год журнала: 2022, Номер 186(5), С. R65 - R77

Опубликована: Фев. 17, 2022

Over the past few years, growing evidence suggests direct crosstalk between thyroid hormones (THs) and immune system. Components of system were proposed to interfere with central regulation systemic TH levels. Conversely, THs regulate innate adaptive responses as cells are target THs. Accordingly, they express different components local action, such transporters or receptors, but our picture interplay is still incomplete. This review provides a critical overview current knowledge regarding interaction main focus on action within major cell subsets. Thereby, this aims highlight open issues which might help infer clinical relevance in host defence context types diseases infection, ischemic organ injury cancer.

Язык: Английский

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Deiodinases and the Metabolic Code for Thyroid Hormone Action

Endocrinology, Год журнала: 2021, Номер 162(8)

Опубликована: Март 15, 2021

Abstract Deiodinases modify the biological activity of thyroid hormone (TH) molecules, ie, they may activate thyroxine (T4) to 3,5,3′-triiodothyronine (T3), or inactivate T3 3,3′-diiodo-L-thyronine (T2) T4 reverse triiodothyronine (rT3). Although evidence deiodination has been available since 1950s, objective TH metabolism was not established until 1970s. The modern paradigm considers that deiodinases only play a role in homeostasis circulating T3, but also provide dynamic control signaling: cells express activating type 2 deiodinase (D2) have enhanced signaling due intracellular build-up T3; opposite is seen 3 (D3), inactivating deiodinase. D2 and D3 are expressed metabolically relevant tissues such as brown adipose tissue, skeletal muscle liver, their roles investigated using cell, animal, human models. During development, expression customize for each tissue/organ timing intensity signaling. In adult cells, induced by cyclic adenosine monophosphate (cAMP), its invariably associated with signaling, PGC1 accelerated energy expenditure. contrast, hypoxia-inducible factor 1α (HIF-1a), dampening metabolic rate. coordinated these enzymes adjusts time- tissue-specific fashion, affecting pathways health disease states.

Язык: Английский

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Selenoproteins in brain development and function

Free Radical Biology and Medicine, Год журнала: 2022, Номер 190, С. 105 - 115

Опубликована: Авг. 10, 2022

Язык: Английский

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