scholarly journals Is respiratory activity in the brain mitochondria responsive to thyroid hormone action?: a critical re-evaluation

1994 ◽  
Vol 302 (3) ◽  
pp. 857-860 ◽  
Author(s):  
S S Katyare ◽  
C S Bangur ◽  
J L Howland
Keyword(s):  
Thyroid Hormone ◽  
Malate Dehydrogenase ◽  
Respiratory Activity ◽  
Hormone Treatment ◽  
Brain Mitochondria ◽  
Dependent Manner ◽  
Glutamate Pyruvate ◽  
Activity State ◽  
Cytochrome Content

The effects of in vivo treatment with graded doses (0.5-1.5 micrograms/g body weight) of thyroid hormones, tri-iodothyronine (T3) and thyroxine (T4), for 4 consecutive days to euthyroid rats on the respiratory activity of isolated brain mitochondria were examined. T4 stimulated coupled State-3 respiration with glutamate, pyruvate + malate, ascorbate + tetramethyl-p-phenylenediamine and succinate, in a dose-dependent manner; T3 was effective only at the highest (1.5 micrograms) dose employed. T4 was more effective than T3 in stimulating respiratory activity. State-4 respiratory rates were in general not influenced except in the case of the ascorbate + tetramethyl-p-phenylenediamine system. Primary dehydrogenase activities, i.e. glutamate dehydrogenase, malate dehydrogenase and succinate dehydrogenase, were stimulated about 2-fold; interestingly mitochondrial but not cytosolic malate dehydrogenase activity was influenced under these conditions. The hormone treatments did not greatly influence the mitochondrial cytochrome content. The results therefore suggest that thyroid hormone treatment not only stimulates primary dehydrogenase activities but may also directly influence the process of mitochondrial electron transfer.

scholarly journals Thyroid Hormone Induces DNA Demethylation in Xenopus Tadpole Brain

Endocrinology ◽  
2020 ◽  
Vol 161 (11) ◽  
Author(s):  
Samhitha Raj ◽  
Yasuhiro Kyono ◽  
Christopher J Sifuentes ◽  
Elvira del Carmen Arellanes-Licea ◽  
Arasakumar Subramani ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Gene Transcription ◽  
Dna Methyltransferase ◽  
Developmental Process ◽  
Brain Regions ◽  
Dna Demethylation ◽  
Dependent Manner ◽  
Messenger Ribonucleic Acid ◽  
Chip Sequencing

Abstract Thyroid hormone (T3) plays pivotal roles in vertebrate development, acting via nuclear T3 receptors (TRs) that regulate gene transcription by promoting post-translational modifications to histones. Methylation of cytosine residues in deoxyribonucleic acid (DNA) also modulates gene transcription, and our recent finding of predominant DNA demethylation in the brain of Xenopus tadpoles at metamorphosis, a T3-dependent developmental process, caused us to hypothesize that T3 induces these changes in vivo. Treatment of premetamorphic tadpoles with T3 for 24 or 48 hours increased immunoreactivity in several brain regions for the DNA demethylation intermediates 5-hydroxymethylcytosine (5-hmC) and 5-carboxylcytosine, and the methylcytosine dioxygenase ten-eleven translocation 3 (TET3). Thyroid hormone treatment induced locus-specific DNA demethylation in proximity to known T3 response elements within the DNA methyltransferase 3a and Krüppel-like factor 9 genes, analyzed by 5-hmC immunoprecipitation and methylation sensitive restriction enzyme digest. Chromatin-immunoprecipitation (ChIP) assay showed that T3 induced TET3 recruitment to these loci. Furthermore, the messenger ribonucleic acid for several genes encoding DNA demethylation enzymes were induced by T3 in a time-dependent manner in tadpole brain. A TR ChIP-sequencing experiment identified putative TR binding sites at several of these genes, and we provide multiple lines of evidence to support that tet2 contains a bona fide T3 response element. Our findings show that T3 can promote DNA demethylation in developing tadpole brain, in part by promoting TET3 recruitment to discrete genomic regions, and by inducing genes that encode DNA demethylation enzymes.

scholarly journals ATP synthase subunit c expression: physiological regulation of the P1 and P2 genes

1997 ◽  
Vol 323 (2) ◽  
pp. 379-385 ◽  
Author(s):  
Ulf ANDERSSON ◽  
Josef HOUŠTĚK ◽  
Barbara CANNON
Keyword(s):  
Thyroid Hormone ◽  
Cold Acclimation ◽  
Atp Synthase ◽  
Hormone Treatment ◽  
Rat Tissues ◽  
Mrna Levels ◽  
Subunit C ◽  
Brown Adipose ◽  
Mitochondrial Atp Synthase

Pre-translational regulation of subunit c has been suggested to control the biosynthesis of mitochondrial ATP synthase (ATPase) in brown adipose tissue (BAT). Subunit c is encoded by the genes P1 and P2, which encode identical mature proteins. We have determined here the levels of P1 and P2 mRNAs in different tissues, in response to cold acclimation in rats, during ontogenic development of BAT in hamsters, and following thyroid hormone treatment in rat BAT and liver. Quantitative ribonuclease protection analysis showed that both the P1 and P2 mRNAs were present in all rat tissues measured. Their total amount in each tissue corresponded well with the ATPase content of that tissue. While the P1/P2 mRNA ratio is high in ATPase-rich tissues, the P2 mRNA dominates in tissues with less ATPase. Cold acclimation affects P1 but not P2 gene expression in rat BAT. A rapid and transient increase in P1 mRNA is followed by sustained depression, which is accompanied by a decrease in ATPase content. Similarly, ontogenic suppression of ATPase content in hamster BAT was accompanied by suppression of the P1 mRNA levels, while P2 expression was virtually unchanged. Furthermore, when hypothyroid rats were treated with thyroid hormone, the steady-state level of P1 but not of P2 mRNA was significantly increased in liver. BAT was unaffected. We conclude that the P1 and P2 genes for subunit c are differentially regulated in vivo. While the P2 gene is expressed constitutively, the P1 gene responds to different physiological stimuli as a means of modulating the relative content of ATP synthase.

scholarly journals Liganded Thyroid Hormone Receptor Induces Nucleosome Removal and Histone Modifications to Activate Transcription during Larval Intestinal Cell Death and Adult Stem Cell Development

Endocrinology ◽  
2012 ◽  
Vol 153 (2) ◽  
pp. 961-972 ◽  
Author(s):  
Kazuo Matsuura ◽  
Kenta Fujimoto ◽  
Liezhen Fu ◽  
Yun-Bo Shi
Keyword(s):  
Cell Death ◽  
Gene Regulation ◽  
Thyroid Hormone ◽  
Chromatin Remodeling ◽  
Histone Modifications ◽  
Intestinal Cell ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Vertebrate Development

Thyroid hormone (T3) plays an important role in regulating multiple cellular and metabolic processes, including cell proliferation, cell death, and energy metabolism, in vertebrates. Dysregulation of T3 signaling results in developmental abnormalities, metabolic defects, and even cancer. We used T3-dependent Xenopus metamorphosis as a model to study how T3 regulates transcription during vertebrate development. T3 exerts its metamorphic effects through T3 receptors (TR). TR recruits, in a T3-dependent manner, cofactor complexes that can carry out chromatin remodeling/histone modifications. Whether and how histone modifications change upon gene regulation by TR during vertebrate development is largely unknown. Here we analyzed histone modifications at T3 target genes during intestinal metamorphosis, a process that involves essentially total apoptotic degeneration of the simple larval epithelium and de novo development of the adult epithelial stem cells, followed by their proliferation and differentiation into the complex adult epithelium. We demonstrated for the first time in vivo during vertebrate development that TR induces the removal of core histones at the promoter region and the recruitment of RNA polymerase. Furthermore, a number of histone activation and repression marks have been defined based on correlations with mRNA levels in cell cultures. Most but not all correlate with gene expression induced by liganded TR during development, suggesting that tissue and developmental context influences the roles of histone modifications in gene regulation. Our findings provide important mechanistic insights on how chromatin remodeling affects developmental gene regulation in vivo.

13 C n. m. r. studies of gluconeogenesis in rat liver suspensions and perfused mouse livers

1980 ◽  
Vol 289 (1037) ◽  
pp. 407-411 ◽  
Keyword(s):  
Thyroid Hormone ◽  
Rat Liver ◽  
Hormone Treatment ◽  
Liver Cells ◽  
First Approximation ◽  
Rat Liver Cells

Our early 31 P n.m.r. studies of compartmentation in suspensions of rat liver cells have been extended by following fructose-1-phosphate peaks, known to be in the cytosol, which gave the same pH as the P 1 peak previously assigned to the cytosol. Gluconeogenesis has been followed from [ 13 C]glycerol labelled at C1,3 or at C2 and from labelled [3- 13 C] alanine. With the glycerol substrate it was possible to follow the label into α-glycerophosphate and to determine its distribution in the glucose formed. To a first approximation (i.e. 90 %) the glucose label could be followed from its original glycerol position, e.g. [ 1,3- 13 C]glycerol to strongly labelled positions 1, 3, 4 and 6 of glucose. Slightly more than 10% of the label was scrambled (i.e. 10% movement of C2 to C1 and ca . 10% of C1 was lost, the remainder being unchanged). These are consistent with a flux through the pentose shunt, dominated by the transketolase pathway. With [3- 13 C]alanine, about 14 resonances are assigned to different carbons of the intermediates β-hydroxybutyrate, acetoacetate, lactate, pyruvate, glutamate, glutamine, asparate, as well as C2-alanine, while another 7 resonances are observed from the different anomeric carbons of glucose. The effects of thyroid hormone treatment of the rats upon numerous in vivo rates are clearly observed and will be illustrated.

High levels of thyroid hormone impair regulatory T cells function via reduced PD-1 expression

2021 ◽  
Author(s):  
Yi Zhong ◽  
Ting-Ting Lu ◽  
Xiao-Mei Liu ◽  
Bing-Li Liu ◽  
Yun Hu ◽  
...  
Keyword(s):  
T Cells ◽  
Thyroid Hormone ◽  
Regulatory T Cells ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear

Abstract Context Regulatory T cells (Tregs) dysfunction plays an important role in the development and progression of Graves’ disease (GD). Programmed cell death 1 (PD-1) prompts FoxP3 in Tregs expression and enhances the suppressive activity of Tregs. Whether abnormal expression of PD-1 contributes to the breakdown of Tregs and the role of thyroid hormone in the PD-1 expression of Tregs in GD remain substantially undefined. Objective To evaluate the role of PD-1 in Tregs function and triiodothyronine (T3) in PD-1 expression in patients with GD and mice treated with T3. Methods We recruited 30 patients with GD and 30 healthy donors. PD-1 expression in Tregs and Tregs function were determined. To evaluate the effects of thyroid hormone on PD-1 expression in Tregs, we used T3 for the treatment of human peripheral blood mononuclear cells (PBMCs). We then treated mice with T3 to confirm the effect of thyroid hormone on PD-1 expression in Tregs and Tregs function in vivo. Results PD-1 expression in Tregs and the suppressive function of Tregs significantly decreased in patients with GD. T3 reduced PD-1 expression in human Tregs in a concentration- and time-dependent manner in vitro. High levels of circulating T3 reduced PD-1 expression in Tregs, impaired Tregs function, and disrupted T-helper cell (Th1 and Th2) balance in mice treated with T3. Conclusions Tregs dysfunction in GD patients might be due to down-regulation of PD-1 expression in Tregs induced by high levels of serum T3.

scholarly journals Regulation of thyroid hormone activation via the liver X-receptor/retinoid X-receptor pathway

2010 ◽  
Vol 205 (2) ◽  
pp. 179-186 ◽  
Author(s):  
Marcelo A Christoffolete ◽  
Márton Doleschall ◽  
Péter Egri ◽  
Zsolt Liposits ◽  
Ann Marie Zavacki ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Liver X Receptor ◽  
Retinoid X Receptor ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Diet Induced Obesity ◽  
Ectopic Liver ◽  
Dose Dependent

Thyroid hormone receptor (TR) and liver X-receptor (LXR) are the master regulators of lipid metabolism. Remarkably, a mouse with a targeted deletion of both LXRα and LXRβ is resistant to western diet-induced obesity, and exhibits ectopic liver expression of the thyroid hormone activating type 2 deiodinase (D2). We hypothesized that LXR/retinoid X-receptor (RXR) signaling inhibits hepatic D2 expression, and studied this using a luciferase reporter containing the human DIO2 (hDIO2) promoter in HepG2 cells. Given that, in contrast to mammals, the chicken liver normally expresses D2, the chicken DIO2 (cDIO2) promoter was also studied. 22(R)-OH-cholesterol negatively regulated hDIO2 in a dose-dependent manner (100 μM, approximately twofold), while it failed to affect the cDIO2 promoter. Truncations in the hDIO2 promoter identified the region −901 to −584 bp as critical for negative regulation. We also investigated if 9-cis retinoic acid (9-cis RA), the ligand for the heterodimeric partner of TR and LXR, RXR, could regulate the hDIO2 promoter. Notably, 9-cis RA repressed the hDIO2 luciferase reporter (1 μM, approximately fourfold) in a dose-dependent manner, while coexpression of an inactive mutant RXR abolished this effect. However, it is unlikely that RXR homodimers mediate the repression of hDIO2 since mutagenesis of a DR-1 at −506 bp did not interfere with 9-cis RA-mediated repression. Our data indicate that hDIO2 transcription is negatively regulated by both 22(R)-OH-cholesterol and 9-cis RA, which is consistent with LXR/RXR involvement. In vivo, the inhibition of D2-mediated tri-iodothyronine (T3) production by cholesterol/9-cis RA could function as a feedback loop, given that T3 decreases hepatic cholesterol levels.

scholarly journals Topical Thyroid Hormone Accelerates Wound Healing in Mice

Endocrinology ◽  
2005 ◽  
Vol 146 (10) ◽  
pp. 4425-4430 ◽  
Author(s):  
Joshua D. Safer ◽  
Tara M. Crawford ◽  
Michael F. Holick
Keyword(s):  
Wound Healing ◽  
Thyroid Hormone ◽  
Topical Application ◽  
Dependent Manner ◽  
Accelerate Wound Healing ◽  
Previous Hypothesis ◽  
Dose Dependent ◽  
Physiologic Role

Although the physiologic role of thyroid hormone in skin is not well understood, mounting evidence suggests that T3 plays an important role in epidermal proliferation. The goal of this project was to evaluate whether the topical application of supraphysiologic doses of T3 could accelerate wound healing. We evaluated mice treated with topical T3vs. the same mice receiving vehicle alone (Novasome A). Ten-millimeter diameter (79 mm2) dorsal skin wounds were established in all animals, and wounds were remeasured 4 d after injury. All animals were evaluated twice: once with the T3 treatment and once with the vehicle alone. Daily topical application of 150 ng T3 resulted in 58% greater wound closure relative to wounds on the same animals receiving vehicle alone (P < 0.001). Furthermore, we determined that wound healing-associated keratin 6 protein expression in hair follicle keratinocytes increased in a dose-dependent manner in vivo during topical T3 treatment. The data support our previous hypothesis that T3 is necessary for optimal wound healing. Now, we further suggest that topical thyroid hormone may be an inexpensive agent to hasten healing of certain wounds.

scholarly journals A Mechanism to Enhance Cellular Responsivity to Hormone Action: Krüppel-Like Factor 9 Promotes Thyroid Hormone Receptor-β Autoinduction During Postembryonic Brain Development

Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1683-1693 ◽  
Author(s):  
Fang Hu ◽  
Joseph R. Knoedler ◽  
Robert J. Denver
Keyword(s):  
Thyroid Hormone ◽  
Gene Transfer ◽  
Target Genes ◽  
Thyroid Hormone Receptor ◽  
Upstream Region ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Functional Dna ◽  
Mutant Forms

Abstract Thyroid hormone (TH) receptor (TR)-β (trb) is induced by TH (autoinduced) in Xenopus tadpoles during metamorphosis. We previously showed that Krüppel-like factor 9 (Klf9) is rapidly induced by TH in the tadpole brain, associates in chromatin with the trb upstream region in a developmental stage and TH-dependent manner, and forced expression of Klf9 in the Xenopus laevis cell line XTC-2 accelerates and enhances trb autoinduction. Here we investigated whether Klf9 can promote trb autoinduction in tadpole brain in vivo. Using electroporation-mediated gene transfer, we transfected plasmids into premetamorphic tadpole brain to express wild-type or mutant forms of Klf9. Forced expression of Klf9 increased baseline trb mRNA levels in thyroid-intact but not in goitrogen-treated tadpoles, supporting that Klf9 enhances liganded TR action. As in XTC-2 cells, forced expression of Klf9 enhanced trb autoinduction in tadpole brain in vivo and also increased TH-dependent induction of the TR target genes klf9 and thbzip. Consistent with our previous mutagenesis experiments conducted in XTC-2 cells, the actions of Klf9 in vivo required an intact N-terminal region but not a functional DNA binding domain. Forced expression of TRβ in tadpole brain by electroporation-mediated gene transfer increased baseline and TH-induced TR target gene transcription, supporting a role for trb autoinduction during metamorphosis. Our findings support that Klf9 acts as an accessory transcription factor for TR at the trb locus during tadpole metamorphosis, enhancing trb autoinduction and transcription of other TR target genes, which increases cellular responsivity to further TH action on developmental gene regulation programs.

scholarly journals SAT-441 Transcriptome Analysis Under Differential Thyroid Hormone Treatment During Mouse Cerebellar Development

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Hiroyuki Yajima ◽  
Ishii Sumiyasu ◽  
Wataru Miyazaki ◽  
Noriyuki Koibuchi
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Thyroid Hormone ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Hormone Treatment ◽  
Cerebellar Development ◽  
Mrna Levels ◽  
Dependent Manner

Abstract Background: Thyroid hormone (TH) plays essential roles in the development of the cerebellum by regulating transcription of target genes. TH binds to TH receptor (TR) located in the cell nucleus and stimulates transcription through TH response element (TRE). The expression of many genes is temporary and spatially regulated by TH during cerebellar development. However, the mode of transcription by TR may vary among target genes. In the liver, different duration of TH exposure resulted in distinct gene expression profiles. To examine the mechanisms of transcriptional regulation by TH in cerebellar development, gene expression profile induced by various TH exposure duration was studied. Methods: Anti-thyroid drug propylthiouracil (250 ppm in drinking water) was administered to C57BL/6J mice from the gestational day 14 to postnatal day (P) 7 to generate perinatal hypothyroid mice. To study the effect of continuous TH exposure, TH was subcutaneously administered to hypothyroid pups from P2 to P7 (6 days group). To study the effect of single TH administration, TH was injected on P7 and mice were sacrificed either 6 (6 hours group) or 24 hours (24 hours group) after injection. Cerebellar samples were collected to extract RNA and subject to microarray analysis. Microarray results were confirmed by RT-qPCR. Results: In microarray result, compared with mRNA levels of hypothyroid mice, 6 days group induced upregulation in 1007 genes and downregulation in 1009 genes, 6 hours group induced upregulation in 355 genes and downregulation in 977 genes, and 24 hours group induced upregulation in 365 genes and downregulation in 1121 genes. Only 7.6% of the genes were overlapped in three groups among positively regulated genes. In contrast, 57.2% of the genes were common in the negatively regulated genes. In RT-qPCR result, among genes known to harbor TRE, Hairless, Pcp2, and Nrgn, showed differential upregulation patterns. Hairless was upregulated in all groups, whereas Pcp2 was upregulated only in 5 days group and Nrgn was not upregulated in all groups. These results suggest that different mode of transcriptional regulation occurred in an exposure time-dependent manner of TH. Conclusion: We identified gene groups whose expression were modified by TH during cerebellar development. TH distinctively regulates transcription of target genes depending on the exposure schedule in mouse developing cerebellum.

Sign in / Sign up

Export Citation Format

Share Document