scholarly journals Thyroid Hormone Regulation of Metabolism

2014 ◽  
Vol 94 (2) ◽  
pp. 355-382 ◽  
Author(s):  
Rashmi Mullur ◽  
Yan-Yun Liu ◽  
Gregory A. Brent
Keyword(s):  
Thyroid Hormone ◽  
Signaling Pathways ◽  
Thyroid Hormone Receptor ◽  
Active Form ◽  
Thyroid Stimulating Hormone ◽  
Peroxisome Proliferator ◽  
Hormone Regulation ◽  
Brown Adipose ◽  
Regulation Of Metabolism ◽  
White Fat

Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5′-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets.

scholarly journals Inhibition of Peroxisome Proliferator Signaling Pathways by Thyroid Hormone Receptor

1997 ◽  
Vol 272 (12) ◽  
pp. 7752-7758 ◽  
Author(s):  
Takahide Miyamoto ◽  
Atsuko Kaneko ◽  
Tomoko Kakizawa ◽  
Hiroki Yajima ◽  
Keiju Kamijo ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Signaling Pathways ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Peroxisome Proliferator

3,5-Diiodothyronine-mediated transrepression of the thyroid hormone receptor beta gene in tilapia. Insights on cross-talk between the thyroid hormone and cortisol signaling pathways

2016 ◽  
Vol 425 ◽  
pp. 103-110 ◽  
Author(s):  
Gabriela Hernández-Puga ◽  
Pamela Navarrete-Ramírez ◽  
Arturo Mendoza ◽  
Aurora Olvera ◽  
Patricia Villalobos ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Signaling Pathways ◽  
Cross Talk ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Beta Gene ◽  
Receptor Beta

scholarly journals Thyroid-hormone-dependent negative regulation of thyrotropin beta gene by thyroid hormone receptors: study with a new experimental system using CV1 cells

2004 ◽  
Vol 378 (2) ◽  
pp. 549-557 ◽  
Author(s):  
Keiko NAKANO ◽  
Akio MATSUSHITA ◽  
Shigekazu SASAKI ◽  
Hiroko MISAWA ◽  
Kozo NISHIYAMA ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptor ◽  
Experimental System ◽  
Thyroid Stimulating Hormone ◽  
Negative Regulation ◽  
Dominant Negative ◽  
Negative Effects ◽  
Receptor Isoforms

The molecular mechanism involved in the liganded thyroid hormone receptor suppression of the TSHβ (thyroid-stimulating hormone β, or thyrotropin β) gene transcription is undetermined. One of the main reasons is the limitation of useful cell lines for the experiments. We have developed an assay system using non-pituitary CV1 cells and studied the negative regulation of the TSHβ gene. In CV1 cells, the TSHβ–CAT (chloramphenicol acetyltransferase) reporter was stimulated by Pit1 and GATA2 and suppressed by T3 (3,3´,5-tri-iodothyronine)-bound thyroid hormone receptor. The suppression was dependent on the amounts of T3 and the receptor. Unliganded receptor did not stimulate TSHβ activity, suggesting that the receptor itself is not an activator. Analyses using various receptor mutants revealed that the intact DNA-binding domain is crucial to the TSHβ gene suppression. Co-activators and co-repressors are not necessarily essential, but are required for the full suppression of the TSHβ gene. Among the three receptor isoforms, β2 exhibited the strongest inhibition and its protein level was the most predominant in a thyrotroph cell line, TαT1, in Western blotting. The dominant-negative effects of various receptor mutants measured on the TSHβ–CAT reporter were not simple mirror images of those in the positive regulation under physiological T3 concentration.

scholarly journals Liver X receptor β controls thyroid hormone feedback in the brain and regulates browning of subcutaneous white adipose tissue

2015 ◽  
Vol 112 (45) ◽  
pp. 14006-14011 ◽  
Author(s):  
Yifei Miao ◽  
Wanfu Wu ◽  
Yubing Dai ◽  
Laure Maneix ◽  
Bo Huang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Thyroid Hormone ◽  
Energy Expenditure ◽  
White Adipose Tissue ◽  
Uncoupling Protein ◽  
Thyroid Stimulating Hormone ◽  
Vital Role ◽  
Normal Diet ◽  
Subcutaneous White Adipose Tissue ◽  
Brown Adipose

The recent discovery of browning of white adipose tissue (WAT) has raised great research interest because of its significant potential in counteracting obesity and type 2 diabetes. Browning is the result of the induction in WAT of a newly discovered type of adipocyte, the beige cell. When mice are exposed to cold or several kinds of hormones or treatments with chemicals, specific depots of WAT undergo a browning process, characterized by highly activated mitochondria and increased heat production and energy expenditure. However, the mechanisms underlying browning are still poorly understood. Liver X receptors (LXRs) are one class of nuclear receptors, which play a vital role in regulating cholesterol, triglyceride, and glucose metabolism. Following our previous finding that LXRs serve as repressors of uncoupling protein-1 (UCP1) in classic brown adipose tissue in female mice, we found that LXRs, especially LXRβ, also repress the browning process of subcutaneous adipose tissue (SAT) in male rodents fed a normal diet. Depletion of LXRs activated thyroid-stimulating hormone (TSH)-releasing hormone (TRH)-positive neurons in the paraventricular nucleus area of the hypothalamus and thus stimulated secretion of TSH from the pituitary. Consequently, production of thyroid hormones in the thyroid gland and circulating thyroid hormone level were increased. Moreover, the activity of thyroid signaling in SAT was markedly increased. Together, our findings have uncovered the basis of increased energy expenditure in male LXR knockout mice and provided support for targeting LXRs in treatment of obesity.

scholarly journals Adaptations of the Autonomous Nervous System Controlling Heart Rate Are Impaired by a Mutant Thyroid Hormone Receptor-α1

Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 2388-2395 ◽  
Author(s):  
Jens Mittag ◽  
Benjamin Davis ◽  
Milica Vujovic ◽  
Anders Arner ◽  
Björn Vennström
Keyword(s):  
Heart Rate ◽  
Nervous System ◽  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Cardiac Activity ◽  
Autonomic Control ◽  
Autonomous Nervous System ◽  
Wild Type ◽  
Brown Adipose

Thyroid hormone has profound direct effects on cardiac function, but the hormonal interactions with the autonomic control of heart rate are unclear. Because thyroid hormone receptor (TR)-α1 has been implicated in the autonomic control of brown adipose energy metabolism, it might also play an important role in the central autonomic control of heart rate. Thus, we aimed to analyze the role of TRα1 signaling in the autonomic control of heart rate using an implantable radio telemetry system. We identified that mice expressing the mutant TRα1R384C (TRα1+m mice) displayed a mild bradycardia, which becomes more pronounced during night activity or on stress and is accompanied by a reduced expression of nucleotide-gated potassium channel 2 mRNA in the heart. Pharmacological blockage with scopolamine and the β-adrenergic receptor antagonist timolol revealed that the autonomic control of cardiac activity was similar to that in wild-type mice at room temperature. However, at thermoneutrality, in which the regulation of heart rate switches from sympathetic to parasympathetic in wild-type mice, TRα1+m mice maintained sympathetic stimulation and failed to activate parasympathetic signaling. Our findings demonstrate a novel role for TRα1 in the adaptation of cardiac activity by the autonomic nervous system and suggest that human patients with a similar mutation in TRα1 might exhibit a deficit in cardiac adaptation to stress or physical activity and an increased sensitivity to β-blockers.

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