TRα inhibits arterial renin-angiotensin system expression and prevents cholesterol accumulation in vascular smooth muscle cells.

Objectives: The tissue renin-angiotensin system (tRAS) plays a key role in the maintenance of cellular homeostasis but is also implicated in atherosclerosis. Thyroid hormone (TH) contributes, via genomic effects, to control of tRAS gene expression in the arterial wall and vascular smooth muscle cells (VSMCs). We investigated the specific functions of TH receptors-α and -β (TRα and TRβ) on tRAS gene expression in the aorta and VSMCs, and the potential protective effect of TRα against atherosclerosis.

Increased expression of the thyroid hormone nuclear receptor TRα1 characterizes intestinal tumors with high Wnt activity.

Our previous work demonstrated a key function of the thyroid hormone nuclear receptor TRα1, a T3-modulated transcription factor, in controlling intestinal development and homeostasis the Wnt and Notch pathways. Importantly, increased expression of TRα1 in the intestinal epithelium in a mutated genetic background (-TRα1/Apc mice) accelerated tumorigenesis and contributed to a more aggressive tumor phenotype compared to that of the mutants alone. Therefore, the aim of this study was to determine the relevance of this synergistic effect in human colorectal cancers and to gain insights into the mechanisms involved.

Thyroid Hormone Receptor Alpha Deletion in ApoE-/- Mice Alters the Arterial Renin-Angiotensin System and Vascular Smooth Muscular Cell Cholesterol Metabolism.

Thyroid hormone (TH) regulates gene transcription by binding to TH receptors (TRs). TRs regulate the genes of lipid metabolism and the renin-angiotensin system (RAS). We examined the effect of TRα deletion in ApoE-/- mice (DKO mice) on the following: (i) the expression of genes controlling cholesterol metabolism and tissue (t)RAS in the liver and aorta and (ii) the expression of these genes and the regulation of cholesterol content in cultured vascular smooth muscle cells (VSMCs).

Thyroid Hormone Receptors: Several Players for One Hormone and Multiple Functions.

Thyroid hormone receptors (TRs) were cloned based on their homology with the retroviral oncogene v-ERBA. In Vertebrates two genes, THRA and THRB, encode respectively many isotypes and isoforms of receptors TRα and TRβ, resulting from alternative splicing and/or internal transcription start sites. We present here a wide overview of this diversity and of their mechanisms of action as transcription regulators, as well as alternative actions through cytoplasmic signaling.

Maternal eating behavior is a major synchronizer of fetal and postnatal peripheral clocks in mice.

Most living organisms show circadian rhythms in physiology and behavior. These oscillations are generated by endogenous circadian clocks, present in virtually all cells where they control key biological processes. To study peripheral clocks in vivo, we developed an original model, the Rev-Luc mouse to follow noninvasively and longitudinally Rev-Luc oscillations in peripheral clocks using in vivo bioluminescence imaging.

Methylcytosine dioxygenase TET3 interacts with thyroid hormone nuclear receptors and stabilizes their association to chromatin.

Thyroid hormone receptors (TRs) are members of the nuclear hormone receptor superfamily that act as ligand-dependent transcription factors. Here we identified the ten-eleven translocation protein 3 (TET3) as a TR interacting protein increasing cell sensitivity to T3. The interaction between TET3 and TRs is independent of TET3 catalytic activity and specifically allows the stabilization of TRs on chromatin.

Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight.

The obesity epidemic is a significant global health issue. Improved understanding of the mechanisms that regulate appetite and body weight will provide the rationale for the design of anti-obesity therapies. Thyroid hormones play a key role in metabolic homeostasis through their interaction with thyroid hormone receptors (TRs), which function as ligand-inducible transcription factors.

Thyroid Hormone Signaling Pathways: Time for a More Precise Nomenclature.

Current literature makes a distinction between two pathways for thyroid hormone signaling: genomic and nongenomic. However, this classification is a source of confusion. We propose a clarification in the nomenclature that may help to avoid unproductive controversies and favor progress in this field of research.

The 5-Hydroxymethylcytosine (5hmC) Reader UHRF2 Is Required for Normal Levels of 5hmC in Mouse Adult Brain and Spatial Learning and Memory.

UHRF2 has been implicated as a novel regulator for both DNA methylation (5mC) and hydroxymethylation (5hmC), but its physiological function and role in DNA methylation/hydroxymethylation are unknown. Here we show that in mice, UHRF2 is more abundantly expressed in the brain and a few other tissues. knock-out mice are viable and fertile and exhibit no gross defect.

miR-135a Inhibits the Invasion of Cancer Cells via Suppression of ERRα.

MicroRNA-135a (miR-135a) down-modulates parameters of cancer progression and its expression is decreased in metastatic breast cancers (as compared to non-metastatic tumors) as well as in prostate tumors relative to normal tissue. These expression and activity patterns are opposite to those of the Estrogen-Related Receptor α (ERRα), an orphan member of the nuclear receptor family. Indeed high expression of ERRα correlates with poor prognosis in breast and prostate cancers, and the receptor promotes various traits of cancer aggressiveness including cell invasion.

Characteristics of patients with late manifestation of resistance thyroid hormone syndrome: a single-center experience.

Resistance to thyroid hormone (RTH) is a rare genetic disease caused by reduced tissue sensitivity to thyroid hormone. The hallmark of RTH is elevated serum levels of thyroid hormone with unsuppressed thyrotropin (TSH). However, the most common form of RTH results from minor defects in the ligand-binding domain or hinge domain of the TRβ gene, resulting in impaired T3-induced transcriptional activity, often showing mild presentation.

Androgen-regulated microRNA-135a decreases prostate cancer cell migration and invasion through downregulating ROCK1 and ROCK2.

Androgen signaling, via the androgen receptor (AR), is crucial in mediating prostate cancer (PCa) initiation and progression. Identifying new downstream effectors of the androgens/AR pathway will allow a better understanding of these mechanisms and could reveal novel biomarkers and/or therapeutic agents to improve the rate of patient survival. We compared the microRNA expression profiles in androgen-sensitive LNCaP cells stimulated or not with 1 nM R1881 by performing a high-throughput reverse transcriptase-quantitative PCR and found that miR-135a was upregulated.

Tagging live cells that express specific peptidase activity with solid-state fluorescence.

A three-component probe harnesses the extraordinary properties of a solid-state fluorophore for the detection of living cells exhibiting a particular peptidase activity. The off-on mode by which the probe operates, the bright fluorescence of the resulting precipitate, and the rapid response allow an exceptional signal-to-background ratio during microscopic imaging. A tertiary carbamate link between the spacer and phenolic fluorophore is at the heart of the probe's long-term stability.

TRα protects against atherosclerosis in male mice: identification of a novel anti-inflammatory property for TRα in mice.

Hypothyroidism is associated with an increased occurrence of atherosclerosis, suggesting some protective role for thyroid hormones (THs). Hypercholesterolemia is one of the major risk factor to develop this disease. Here, we show that the well-known TH cholesterol lowering effect was dependent on TH nuclear receptor (TR)β liver activity.

Fluorescent push-pull pH-responsive probes for ratiometric detection of intracellular pH.

A family of fluorescent push-pull pH-responsive probes based on 2-dicyanomethylidene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran as a strong electron acceptor group is described. Small structural variations allow obtaining pK(a) ranging from 4.8 to 8.

Subcellular localization of ENS-1/ERNI in chick embryonic stem cells.

The protein of retroviral origin ENS-1/ERNI plays a major role during neural plate development in chick embryos by controlling the activity of the epigenetic regulator HP1γ, but its function in the earlier developmental stages is still unknown. ENS-1/ERNI promoter activity is down-regulated upon differentiation but the resulting protein expression has never been examined. In this study, we present the results obtained with custom-made antibodies to gain further insights into ENS-1 protein expression in Chicken embryonic stem cells (CES) and during their differentiation.

The targeted inactivation of TRβ gene in thyroid follicular cells suggests a new mechanism of regulation of thyroid hormone production.

Thyroid epithelial cells, or thyrocytes, express functional thyroid hormone receptors but no precise role has yet been assigned to either TRα or TRβ in the thyroid gland. In this study, we analyzed the impact of inactivating the TRβ gene in the thyroid of mice. First, we generated a mouse line named Thyr-Cre, expressing the Cre recombinase under the control of the thyroglobulin gene promoter, which led to a complete recombination of floxed genes in thyrocytes.

Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer.

Background: Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa) among androgen-regulated genes (ARG) and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely) give rise to cancer.

Methods: ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR.

Direct cooperation between androgen receptor and E2F1 reveals a common regulation mechanism for androgen-responsive genes in prostate cells.

We have studied the regulation of ATAD2 gene expression by androgens in prostate cells. ATAD2 is a coactivator of the androgen receptor (AR) and the MYC protein. We showed that ATAD2 expression is directly regulated by AR via an AR binding sequence (ARBS) located in the distal enhancer of its regulatory region.

The endogenous retrovirus ENS-1 provides active binding sites for transcription factors in embryonic stem cells that specify extra embryonic tissue.

Background: Long terminal repeats (LTR) from endogenous retroviruses (ERV) are source of binding sites for transcription factors which affect the host regulatory networks in different cell types, including pluripotent cells. The embryonic epiblast is made of pluripotent cells that are subjected to opposite transcriptional regulatory networks to give rise to distinct embryonic and extraembryonic lineages. To assess the transcriptional contribution of ERV to early developmental processes, we have characterized in vitro and in vivo the regulation of ENS-1, a host adopted and developmentally regulated ERV that is expressed in chick embryonic stem cells.

TM4SF1, a novel primary androgen receptor target gene over-expressed in human prostate cancer and involved in cell migration.

Background: The Androgen Receptor (AR) plays a key role in controlling prostate gland homeostasis and contributes to prostate carcinogenesis. The identification of its target genes should provide new candidates that may be implicated in cancer initiation and progression.

Methods: Transcriptomic experiments and chromatin immunoprecipitation were combined to identify direct androgen regulated genes.

An electroneutral macrocyclic iron(II) complex that enhances MRI contrast in vivo.

The first example of a macrocyclic ferrous complex, where two tetrazolyl pendent arms compensate the charge of the metal center, is synthesized and examined for its capacity to enhance MRI contrast in vitro and in vivo in the mouse.