scholarly journals Sensory Neuron Sodium Current Requires Nongenomic Actions of Thyroid Hormone During Development

2008 ◽  
Vol 100 (5) ◽  
pp. 2719-2725 ◽  
Author(s):  
Marc A. Yonkers ◽  
Angeles B. Ribera
Keyword(s):  
Thyroid Hormone ◽  
Time Course ◽  
Sodium Current ◽  
Active Form ◽  
Hormone Regulation ◽  
Zebrafish Model ◽  
Sodium Conductance ◽  
Rapid Effect ◽  
Touch Response

Development of the embryonic nervous system requires thyroid hormone. However, the underlying mechanisms and targets of thyroid hormone action are not well defined. To identify embryonic roles for thyroid hormone we tested for effects on a key neuronal trait, voltage-gated sodium current ( INa), in the zebrafish model system. We recorded from Rohon–Beard sensory neurons (RBs) using whole cell voltage-clamp methods. Here, we provide in vivo evidence for thyroid hormone regulation of INa. Chronic thyroid hormone application increased RB peak INa density 1.4-fold. However, INa density showed a similar increase within 5 min of an acute hormone application, a time course not expected for a genomic mechanism. Tetraiodothyroacetic acid (tetrac), a thyroid hormone blocker, blocked both chronic and acute effects. Further, the thyroid hormone precursor thyroxine (T4) affected INa, yet the traditionally active form triiodothyronine did not. Consequently, we tested for a nonconventional T4 receptor. LM609, a selective antagonist of integrin αVβ3, occluded the rapid effect of T4, implicating a specific integrin dimer as a T4 receptor. Chronic application of either tetrac or LM609 significantly reduced sodium conductance, demonstrating an in vivo requirement for T4-integrin regulation of INa. Further, removing endogenous T4 levels via yolkectomy reduced sodium conductance, an effect that was partially rescued by T4 supplementation following surgery. Because RBs mediate the embryonic touch response, we tested for behavioral effects. Tetrac and LM609 significantly reduced the percentage of touch trials eliciting a normal touch response. T4's rapid effect on RB INa highlights the importance of embryonic T4 availability and nongenomic T4 signaling.

scholarly journals A Larval Zebrafish Model for Assessing Hypoxic‐Induced In Vivo Cardiomyocyte Damage: Time Course for Induction and Cardiac Output Recovery

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Warren Burggren ◽  
Regina Abramova ◽  
Naim Bautista ◽  
Regina Fritsche Danielson ◽  
Avi Gupta ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Time Course ◽  
Zebrafish Model ◽  
Larval Zebrafish

scholarly journals Identical Gene Regulation Patterns of T3 and Selective Thyroid Hormone Receptor Modulator GC-1

Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 501-511 ◽  
Author(s):  
Chaoshen Yuan ◽  
Jean Z.H. Lin ◽  
Douglas H. Sieglaff ◽  
Steven D. Ayers ◽  
Frances DeNoto-Reynolds ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Hepatoma Cell ◽  
Active Form ◽  
Hepatoma Cell Line ◽  
Beneficial Effects ◽  
Receptor Modulator ◽  
Identical Gene

Synthetic selective thyroid hormone (TH) receptor (TR) modulators (STRM) exhibit beneficial effects on dyslipidemias in animals and humans and reduce obesity, fatty liver, and insulin resistance in preclinical animal models. STRM differ from native TH in preferential binding to the TRβ subtype vs. TRα, increased uptake into liver, and reduced uptake into other tissues. However, selective modulators of other nuclear receptors exhibit important gene-selective actions, which are attributed to differential effects on receptor conformation and dynamics and can have profound influences in animals and humans. Although there are suggestions that STRM may exhibit such gene-specific actions, the extent to which they are actually observed in vivo has not been explored. Here, we show that saturating concentrations of the main active form of TH, T3, and the prototype STRM GC-1 induce identical gene sets in livers of euthyroid and hypothyroid mice and a human cultured hepatoma cell line that only expresses TRβ, HepG2. We find one case in which GC-1 exhibits a modest gene-specific reduction in potency vs. T3, at angiopoietin-like factor 4 in HepG2. Investigation of the latter effect confirms that GC-1 acts through TRβ to directly induce this gene but this gene-selective activity is not related to unusual T3-response element sequence, unlike previously documented promoter-selective STRM actions. Our data suggest that T3 and GC-1 exhibit almost identical gene regulation properties and that gene-selective actions of GC-1 and similar STRM will be subtle and rare.

scholarly journals Thyroid Hormone Regulation of Hepatic Genes in Vivo Detected by Complementary DNA Microarray

2000 ◽  
Vol 14 (7) ◽  
pp. 947-955 ◽  
Author(s):  
Xu Feng ◽  
Yuan Jiang ◽  
Paul Meltzer ◽  
Paul M. Yen
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Cdna Microarray ◽  
Hormonal Regulation ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Hormone Regulation ◽  
Diverse Range ◽  
Hepatic Genes

Abstract The liver is an important target organ of thyroid hormone. However, only a limited number of hepatic target genes have been identified, and little is known about the pattern of their regulation by thyroid hormone. We used a quantitative fluorescent cDNA microarray to identify novel hepatic genes regulated by thyroid hormone. Fluorescent-labeled cDNA prepared from hepatic RNA of T3-treated and hypothyroid mice was hybridized to a cDNA microarray, representing 2225 different mouse genes, followed by computer analysis to compare relative changes in gene expression. Fifty five genes, 45 not previously known to be thyroid hormone-responsive genes, were found to be regulated by thyroid hormone. Among them, 14 were positively regulated by thyroid hormone, and unexpectedly, 41 were negatively regulated. The expression of 8 of these genes was confirmed by Northern blot analyses. Thyroid hormone affected gene expression for a diverse range of cellular pathways and functions, including gluconeogenesis, lipogenesis, insulin signaling, adenylate cyclase signaling, cell proliferation, and apoptosis. This is the first application of the microarray technique to study hormonal regulation of gene expression in vivo and should prove to be a powerful tool for future studies of hormone and drug action.

scholarly journals A thyroid hormone receptor mutation that dissociates thyroid hormone regulation of gene expression in vivo

2009 ◽  
Vol 106 (23) ◽  
pp. 9441-9446 ◽  
Author(s):  
D. S. Machado ◽  
A. Sabet ◽  
L. A. Santiago ◽  
A. R. Sidhaye ◽  
M. I. Chiamolera ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Regulation Of Gene Expression ◽  
Hormone Regulation

scholarly journals Vitamin D Promotes Skeletal Muscle Regeneration and Mitochondrial Health

2021 ◽  
Vol 12 ◽  
Author(s):  
Christine M. Latham ◽  
Camille R. Brightwell ◽  
Alexander R. Keeble ◽  
Brooke D. Munson ◽  
Nicholas T. Thomas ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vitamin D ◽  
Muscle Damage ◽  
Muscle Regeneration ◽  
Muscle Injury ◽  
Time Course ◽  
Active Form ◽  
Skeletal Muscle Regeneration ◽  
Optimal Timing

Vitamin D is an essential nutrient for the maintenance of skeletal muscle and bone health. The vitamin D receptor (VDR) is present in muscle, as is CYP27B1, the enzyme that hydroxylates 25(OH)D to its active form, 1,25(OH)D. Furthermore, mounting evidence suggests that vitamin D may play an important role during muscle damage and regeneration. Muscle damage is characterized by compromised muscle fiber architecture, disruption of contractile protein integrity, and mitochondrial dysfunction. Muscle regeneration is a complex process that involves restoration of mitochondrial function and activation of satellite cells (SC), the resident skeletal muscle stem cells. VDR expression is strongly upregulated following injury, particularly in central nuclei and SCs in animal models of muscle injury. Mechanistic studies provide some insight into the possible role of vitamin D activity in injured muscle. In vitro and in vivo rodent studies show that vitamin D mitigates reactive oxygen species (ROS) production, augments antioxidant capacity, and prevents oxidative stress, a common antagonist in muscle damage. Additionally, VDR knockdown results in decreased mitochondrial oxidative capacity and ATP production, suggesting that vitamin D is crucial for mitochondrial oxidative phosphorylation capacity; an important driver of muscle regeneration. Vitamin D regulation of mitochondrial health may also have implications for SC activity and self-renewal capacity, which could further affect muscle regeneration. However, the optimal timing, form and dose of vitamin D, as well as the mechanism by which vitamin D contributes to maintenance and restoration of muscle strength following injury, have not been determined. More research is needed to determine mechanistic action of 1,25(OH)D on mitochondria and SCs, as well as how this action manifests following muscle injury in vivo. Moreover, standardization in vitamin D sufficiency cut-points, time-course study of the efficacy of vitamin D administration, and comparison of multiple analogs of vitamin D are necessary to elucidate the potential of vitamin D as a significant contributor to muscle regeneration following injury. Here we will review the contribution of vitamin D to skeletal muscle regeneration following injury.

The developmental switch in ventricular myosin expression in vivo is not triggered by an increase in cyclic AMP

1995 ◽  
Vol 7 (5) ◽  
pp. 1361 ◽  
Author(s):  
F Schachat ◽  
FJ Seidler ◽  
TA Slotkin
Keyword(s):  
Thyroid Hormone ◽  
Cyclic Amp ◽  
Acute Treatment ◽  
Time Course ◽  
Developmental Change ◽  
Relative Rate ◽  
Rapid Change ◽  
Pulse Labelling ◽  
Ventricular Myosin

Ventricular myosin heavy chain (HC) expression undergoes a rapid change from the beta to the alpha isoform shortly after birth. Thyroid hormone is required for this transition to occur, but the time course of developmental changes in circulating thyroid hormone levels suggests that it cannot be the trigger for this event. In this study, the possibility was examined that cyclic AMP (cAMP), either acting separately or as a mediator of the permissive actions of thyroid hormone, triggers the developmental transition in ventricular myosin HC expression. One-day-old euthyroid or propylthiouracil-hypothyroid rat pups were treated with a membrane-permeable cAMP analogue, 8-bromo-cAMP (8-Br-cAMP) or triiodothyronine (T3). Two and four hours after acute treatment, the relative synthetic rates of alpha and beta myosin HC were measured using an in vivo pulse labelling technique. Myosin HC isoforms were separated electrophoretically and then quantitated by densitometry. Acute treatment in vivo with 8-Br-cAMP did not alter the relative rate of alpha myosin HC synthesis in euthyroid animals at either 2 or 4 h. Hypothyroidism significantly reduced the relative rate of alpha HC synthesis and obturated the transition from beta to alpha HC. The effect on synthesis was rapidly reversed by acute treatment with T3, but not with 8-Br-cAMP. Thus, an increase in cAMP does not appear to trigger the developmental change in myosin isoform expression, nor does it appear to mediate the stimulatory effect of thyroid hormone on alpha myosin HC synthesis. Instead, thyroid hormone is likely to be acting directly on the alpha HC gene by binding to the thyroid response element. The identity of stimuli that mediate the increased responsiveness to thyroid hormone during development remains to be determined, but it is not due to an increase in the levels of cAMP in perinatal cardiocytes in vivo.

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.

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