A Thyroid Hormone Antagonist That Inhibits Thyroid Hormone Action in Vivo

Lim, Wayland; Nguyen, Ngoc Ha; Yang, Ha Yung; Scanlan, Thomas S.; Furlow, J. David

doi:10.1074/jbc.m205608200

Cited by 104 publications

(109 citation statements)

References 35 publications

(35 reference statements)

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“…From parallel cultures, cell pellets were stored at À801C for Q-PCR. To study receptor-mediated effects, NH-3 (10 mmol/L) was added to T3-treated wells and concentration on the basis of a previous study (Lim et al, 2002). The medium was collected and stored at À801C for quantification of VEGF-A and FGF-2 protein secretion.…”

Section: Rbe4 Cells Expansion Assaymentioning

confidence: 99%

Stimulatory Effects of Thyroid Hormone on Brain Angiogenesis in vivo and in vitro

Zhang

Cooper-Kuhn

Nannmark

et al. 2009

J Cereb Blood Flow Metab

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Thyroid hormone is critical for the proper development of the central nervous system. However, the specific role of thyroid hormone on brain angiogenesis remains poorly understood. Treatment of rats from birth to postnatal day 21 (P21) with propylthiouracil (PTU), a reversible blocker of triiodothyronine (T3) synthesis, resulted in decreased brain angiogenesis, as indicated by reduced complexity and density of microvessels. However, when PTU was withdrawn at P22, these parameters were fully recovered by P90. These changes were paralleled by an altered expression of vascular endothelial growth factor A (Vegfa) and basic fibroblast growth factor (Fgf2). Physiologic concentrations of T3 and thyroxine (T4) stimulated proliferation and tubulogenesis of rat brainderived endothelial (RBE4) cells in vitro. Protein and mRNA levels of VEGF-A and FGF-2 increased after T3 stimulation of RBE4 cells. The thyroid hormone receptor blocker NH-3 abolished T3-induced Fgf2 and Vegfa upregulation, indicating a receptor-mediated effect. Thyroid hormone inhibited the apoptosis in RBE4 cells and altered mRNA levels of apoptosis-related genes, namely Bcl2 and Bad. The present results show that thyroid hormone has a substantial impact on vasculature development in the brain. Pathologically altered vascularization could, therefore, be a contributing factor to the neurologic deficits induced by thyroid hormone deficiency.

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Section: Rbe4 Cells Expansion Assaymentioning

confidence: 99%

Stimulatory Effects of Thyroid Hormone on Brain Angiogenesis in vivo and in vitro

Zhang

Cooper-Kuhn

Nannmark

et al. 2009

J Cereb Blood Flow Metab

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“…However, many other hypotheses can be proposed, since in vivo functional experiments are still to be completed. The use of specific TR agonists and antagonists (Chiellini et al, 1998;Lim et al, 2002;Nguyen et al, 2002) could help deciphering the specific role of TR in this inverted situation.…”

Section: Evolution Of Metamorphosis In Other Vertebrates: Why Direct mentioning

confidence: 99%

The history of a developmental stage: Metamorphosis in chordates

Paris

Laudet

2008

Genesis

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Summary: Metamorphosis displays a striking diversity in chordates, a deuterostome phylum that comprises vertebrates, urochordates (tunicates), and cephalochordates (amphioxus). In anuran amphibians, the tadpole loses its tail, develops limbs, and undergoes profound changes at the behavioral, physiological, biochemical, and ecological levels. In ascidian tunicates, the tail is lost and the head tissues are drastically remodeled into the adult animal, whereas in amphioxus, the highly asymmetric larva transforms into a relatively symmetric adult. This wide diversity has led to the proposal that metamorphosis evolved several times independently in the different chordate lineages during evolution. However, the molecular mechanisms involved in metamorphosis are largely unknown outside amphibians and teleost fishes, in which metamorphosis is regulated by the thyroid hormones (TH) T 3 and T 4 binding to their receptors (thyroid hormone receptors). In this review, we compare metamorphosis in chordates and then propose a unifying definition of the larva-to-adult transition, based on the conservation of the role of THs and some of their derivatives as the main regulators of metamorphosis. According to this definition, all chordates (if not, all deuterostomes) have a homologous metamorphosis stage during their postembryonic development. The intensity and the nature of the morphological remodeling varies extensively among taxa, from drastic remodeling like in some ascidians or amphibians to more subtle events, as in mammals. genesis 46:657-672,

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“…NH-3 is a TR antagonist that strongly inhibits transcriptional activation by T 3 (260)(261)(262)(263)(264)(265). Treatment with this compound has been shown to block thyroid hormone dependent processes such as spontaneous Xenopus laevis tadpole metamorphosis.…”

Section: And Recommendation 25amentioning

confidence: 99%