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

2020 ◽  
Vol 21 (11) ◽  
pp. 4140 ◽  
Author(s):  
Marco Giammanco ◽  
Carlo Maria Di Liegro ◽  
Gabriella Schiera ◽  
Italia Di Liegro
Keyword(s):  
Thyroid Hormones ◽  
Direct Action ◽  
Mechanisms Of Action ◽  
Metabolic Effects ◽  
Clinical Use ◽  
Increase Energy Expenditure ◽  
General Metabolism ◽  
Tissue Damages ◽  
Genomic Effects ◽  
Obesity Drugs

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

scholarly journals Metabolic effects of 3,5-Diiodo-L-Thyronine

2021 ◽  
Vol 93 (2) ◽  
Author(s):  
Marco Giammanco ◽  
Manfredi Marco Giammanco ◽  
Gaetano Leto ◽  
Herbert R. Marini
Keyword(s):  
Hepatic Steatosis ◽  
Metabolic Effects ◽  
Obesity And Overweight ◽  
Increase Energy Expenditure ◽  
Concomitant Reduction ◽  
Tissue Damages ◽  
Hyperlipidic Diet ◽  
Obese Subjects ◽  
Obesity Drugs

Thyroid hormones have been proposed as anti obesity drugs due to their effects on basal metabolism and the ability to increase energy expenditure. However, their clinical use has been strongly curbed by the concomitant onset of thyrotoxicosis. In this setting, several studies have been undertaken to assess the role of 3,5 diiodo- L-thyronine (T2), an endogenous metabolite of thyroid hormone derived from the enzymatic deiodination of triodothyronine T3. The metabolic effects of T2 are similar to those induced by T3. However, these effects appear to involve different and not welldefined mechanisms that make this molecule clinically useful as potential drug in the treatment of pathological conditions such as obesity and hepatic steatosis. The main pharmacological target of T2 appears to be the mitochondria. Therefore, the administration of T2 to obese subjects might improve the mitochondrial performance, which is generally recognized to be reduced in these subjects who must oxidize greater quantities of substrates. In this context, it can be hypothesized that T2, by acting mainly on mitochondrial function and oxidative stress, might be able to prevent and revert the tissue damages and hepatic steatosis induced by a hyperlipidic diet and a concomitant reduction in the circulating levels LDL and triglycerides as well. This review the discuss the mechanisms of action of T2 and the possible, future clinical uses of T2 analogs for the treatment lipid dysmetabolism related to obesity and overweight.

Acute lngestions of Thyroid Hormones

PEDIATRICS ◽  
1984 ◽  
Vol 73 (3) ◽  
pp. 313-317
Author(s):  
Lawrence M. Lehrner ◽  
Michael R. Weir
Keyword(s):  
Thyroid Hormones ◽  
Activated Charcoal ◽  
Exchange Transfusion ◽  
Enterohepatic Circulation ◽  
Case Reports ◽  
Mechanisms Of Action ◽  
Metabolic Effects ◽  
Cellular Mechanisms ◽  
Toxic Potential

Although thyroid medications are commonly prescribed, there are only nine case reports describing the consequences of acute excessive ingestion of thyroid hormones. Two additional cases are presented and the prior nine cases are reviewed. The potential for toxicity is discussed in relationship to the cellular mechanisms of action of thyroid hormones. Although the potential for toxicity is low, the following therapy is recommended to decrease further the toxic potential: (1) lavage and activated charcoal to decrease absorption, (2) cholestyramine to decrease enterohepatic circulation (3) prednisone and/or propylthiouracil to decrease conversion of thyroxine to triiodothyronine, and (4) propranolol to block metabolic effects. If symptoms of toxicity develop, then attempts to remove thyroid hormones should be undertaken using exchange transfusion.

Non-genomic effects of thyroid hormones on endothelial cell tube formation

2016 ◽  
Author(s):  
Kathrin A Schmohl ◽  
Maike Dohmann ◽  
Alexandra Wechselberger ◽  
Peter J Nelson ◽  
Christine Spitzweg
Keyword(s):  
Endothelial Cell ◽  
Thyroid Hormones ◽  
Tube Formation ◽  
Genomic Effects

scholarly journals Involvement of Thyroid Hormones in Brain Development and Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2693
Author(s):  
Gabriella Schiera ◽  
Carlo Maria Di Liegro ◽  
Italia Di Liegro
Keyword(s):  
Nervous System ◽  
Thyroid Hormones ◽  
Brain Development ◽  
Placental Transfer ◽  
Regulation Of Gene Expression ◽  
Mammalian Brain ◽  
Cancer Proliferation ◽  
Fetal Thyroid ◽  
Genomic Effects ◽  
And Function

The development and maturation of the mammalian brain are regulated by thyroid hormones (THs). Both hypothyroidism and hyperthyroidism cause serious anomalies in the organization and function of the nervous system. Most importantly, brain development is sensitive to TH supply well before the onset of the fetal thyroid function, and thus depends on the trans-placental transfer of maternal THs during pregnancy. Although the mechanism of action of THs mainly involves direct regulation of gene expression (genomic effects), mediated by nuclear receptors (THRs), it is now clear that THs can elicit cell responses also by binding to plasma membrane sites (non-genomic effects). Genomic and non-genomic effects of THs cooperate in modeling chromatin organization and function, thus controlling proliferation, maturation, and metabolism of the nervous system. However, the complex interplay of THs with their targets has also been suggested to impact cancer proliferation as well as metastatic processes. Herein, after discussing the general mechanisms of action of THs and their physiological effects on the nervous system, we will summarize a collection of data showing that thyroid hormone levels might influence cancer proliferation and invasion.

scholarly journals Direct AMPK Activation Corrects NASH in Rodents Through Metabolic Effects and Direct Action on Inflammation and Fibrogenesis

2021 ◽  
Author(s):  
Pascale Gluais‐Dagorn ◽  
Marc Foretz ◽  
Gregory R. Steinberg ◽  
Battsetseg Batchuluun ◽  
Anna Zawistowska‐Deniziak ◽  
...  
Keyword(s):  
Direct Action ◽  
Metabolic Effects ◽  
Ampk Activation

Prospects for immunomodulatory therapy of bronchial asthma

1998 ◽  
Vol 79 (5) ◽  
pp. 388-391
Author(s):  
G. V. Cherepnev ◽  
Y. D. Slabnov ◽  
I. E. Zimakova
Keyword(s):  
Bronchial Asthma ◽  
Russian Federation ◽  
Mechanisms Of Action ◽  
Immunomodulatory Therapy ◽  
Immune Homeostasis ◽  
Clinical Use ◽  
Immunological Reactivity ◽  
The Past ◽  
The Russian Federation ◽  
Pharmacological Correction

The relevance of pharmacological correction of immunological reactivity is obvious: many socially significant diseases are accompanied by an imbalance in immune homeostasis. In the past few years, a number of reviews on the classification and mechanisms of action of immunotropic drugs approved for clinical use in the Russian Federation have been published in the domestic press.

Thyroid Stimulating Immunoglobulins: Measurement and Clinical use

1985 ◽  
Vol 69 (2) ◽  
pp. 113-121 ◽  
Author(s):  
C. A. Ollis ◽  
S. Tomlinson ◽  
D. S. Munro
Keyword(s):  
Thyroid Hormones ◽  
Elevated Serum ◽  
Serum Levels ◽  
The Other ◽  
Graves Disease ◽  
Clinical Use ◽  
Hormone Production ◽  
Skin Changes ◽  
Thyroid Stimulating Immunoglobulins ◽  
Eye Involvement

Graves’ disease is the commonest form of hyperthyroidism in which excessive production of thyroid hormones by the hyperplastic overactive thyroid gland produces elevated serum levels of the thyroid hormones tri-iodothyronine (T3) and thyroxine (T4). Many of the manifestations of Graves’ disease, increased basal metabolic rate, increased heart rate, heat intolerance, sweating and nervousness, can be attributed to the peripheral actions of the excess thyroid hormones. The pathogenesis of many of the other dramatic features of Graves’ disease, such as the eye involvement or localized skin changes, is not fully understood, but circulating immunoglobulins with thyroid stimulating activity are almost certainly linked to excess thyroid hormone production and thereby cause the hyperthyroidism.

Polyphenols: Novel Signaling Pathways

2018 ◽  
Vol 24 (2) ◽  
pp. 158-170 ◽  
Author(s):  
Marie-Louise Ricketts ◽  
Bradley S. Ferguson
Keyword(s):  
Risk Factors ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Density Lipoprotein ◽  
Mechanisms Of Action ◽  
Metabolic Effects ◽  
Special Focus ◽  
In Vivo Models ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome

Background: Cardiovascular disease (CVD) is currently the leading cause of death globally. The metabolic syndrome (MetS), a clustering of risk factors including hypertension, hyperglycemia, elevated low-density lipoprotein (LDL) cholesterol, reduced high-density lipoprotein (HDL) cholesterol and increased visceral adiposity, is a significant risk factor for the development of CVD. Non-alcoholic fatty liver disease (NAFLD), often referred to as the hepatic manifestation of MetS, is a constellation of progressive liver disorders closely linked to obesity, diabetes, and insulin resistance. NAFLD initially presents as relatively benign, non-progressive hepatic steatosis, but it may, in certain individuals, progress to nonalcoholic steatohepatitis, fibrosis, cirrhosis, or hepatocellular carcinoma. Currently, there are no validated treatments for NAFLD. Polyphenols are important bioactive dietary compounds and may represent a natural complementary and integrative therapy for the treatment of CVDassociated risk factors, including elevated serum cholesterol and triglyceride levels, as well as NAFLD. Understanding their molecular mechanisms of action is important in the design of future human intervention studies. Methods: Several studies utilizing in vitro and in vivo models have helped to identify underlying molecular mechanisms of action of polyphenols. Results: This review will highlight recent advances regarding the molecular actions of dietary procyanidins, with a special focus on those originating from procyanidin-rich grape seed extracts, with a focus on the signaling pathways utilized to exert beneficial metabolic effects. Conclusion: Modulation of nuclear receptor activity and histone deacetylase inhibition has been identified as underlying mechanisms contributing to procyanidin-mediated amelioration of dyslipidemia and steatosis.

Stimulants and Other ADHD Medicines

2020 ◽  
pp. 231-266
Author(s):  
Arash Ansari ◽  
David N. Osser
Keyword(s):  
Eating Disorder ◽  
Clinical Characteristics ◽  
Mechanisms Of Action ◽  
Black Box ◽  
Brand Names ◽  
Clinical Use ◽  
Childbearing Age ◽  
Hyperactivity Disorder ◽  
Medical Disorders ◽  
Black Box Warnings

The chapter on adult attention-deficit/hyperactivity disorder (ADHD) medicines discusses and reviews the use of psychostimulants (such as methylphenidate and amphetamines), and nonstimulants (such as atomoxetine, guanfacine, and clonidine). It reviews their mechanisms of action, clinical characteristics, potential medication interactions, and adverse effects. It further reviews stimulants’ risk of misuse and dependence. The chapter also briefly discusses complementary and alternative pharmacotherapies. It includes an in-depth review of the clinical use of these medications for ADHD (particularly in college students) and for other psychiatric disorders (such as binge-eating disorder) and other medical disorders. It also discusses the use of ADHD medicines in women of childbearing age, notably for pregnancy and breastfeeding considerations. Finally, the chapter includes a table of ADHD medicines that includes each medicine’s generic and brand names, usual adult doses, pertinent clinical comments, black box warnings, and Food and Drug Administration indications.

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