Regulation of Thyroid Hormone Levels by Hypothalamic Thyrotropin-Releasing Hormone Neurons.

Thyrotropin-releasing hormone (TRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) have been identified as direct regulators of thyrotropin (TSH) and thyroid hormone (TH) levels. They play a significant role in context of negative feedback by TH at the level of TRH gene expression and during fasting when TH levels fall due, in part, to suppression of TRH gene expression. To test these functions directly for the first time, we used a chemogenetic approach and activated PVN TRH neurons in both fed and fasted mice.

Hypothyroidism Induces Hypophagia Associated with Alterations in Protein Expression of Neuropeptide Y and Proopiomelanocortin in the Arcuate Nucleus, Independently of Hypothalamic Nuclei-Specific Changes in Leptin Signaling.

Background: Thyroid hormone and leptin are essential regulators of energy homeostasis. Both hormones stimulate energy expenditure but have opposite effects on appetite. The mechanisms behind food intake regulation in thyroid dysfunctions are poorly understood.

Hepatic nuclear corepressor 1 regulates cholesterol absorption through a TRβ1-governed pathway.

Transcriptional coregulators are important components of nuclear receptor (NR) signaling machinery and provide additional mechanisms for modulation of NR activity. Expression of a mutated nuclear corepressor 1 (NCoR1) that lacks 2 NR interacting domains (NCoRΔID) in the liver leads to elevated expression of genes regulated by thyroid hormone receptor (TR) and liver X receptor (LXR), both of which control hepatic cholesterol metabolism. Here, we demonstrate that expression of NCoRΔID in mouse liver improves dietary cholesterol tolerance in an LXRα-independent manner.

Thyroid hormone signaling in vivo requires a balance between coactivators and corepressors.

Resistance to thyroid hormone (RTH), a human syndrome, is characterized by high thyroid hormone (TH) and thyroid-stimulating hormone (TSH) levels. Mice with mutations in the thyroid hormone receptor beta (TRβ) gene that cannot bind steroid receptor coactivator 1 (SRC-1) and Src-1(-/-) mice both have phenotypes similar to that of RTH. Conversely, mice expressing a mutant nuclear corepressor 1 (Ncor1) allele that cannot interact with TRβ, termed NCoRΔID, have low TH levels and normal TSH.

Novel mechanism of positive versus negative regulation by thyroid hormone receptor β1 (TRβ1) identified by genome-wide profiling of binding sites in mouse liver.

Triiodothyronine (T3) regulates key metabolic processes in the liver through the thyroid hormone receptor, TRβ1. However, the number of known target genes directly regulated by TRβ1 is limited, and the mechanisms by which positive and especially negative transcriptional regulation occur are not well understood. To characterize the TRβ1 cistrome in vivo, we expressed a biotinylated TRβ1 in hypo- and hyperthyroid mouse livers, used ChIP-seq to identify genomic TRβ1 targets, and correlated these data with gene expression changes.

The thyroid axis is regulated by NCoR1 via its actions in the pituitary.

TSH is the most important biomarker in the interpretation of thyroid function in man. Its levels are determined by circulating thyroid hormone (TH) levels that feed back centrally to regulate the expression of the subunits that comprise TSH from the pituitary. The nuclear corepressor 1 (NCoR1), is a critical coregulator of the TH receptor (TR) isoforms.

Hypothyroidism reduces ObRb-STAT3 leptin signalling in the hypothalamus and pituitary of rats associated with resistance to leptin acute anorectic action.

Leptin has been shown to regulate the hypothalamus-pituitary-thyroid axis, acting primarily through the STAT3 pathway triggered through the binding of leptin to the long-chain isoform of the leptin receptor, ObRb. We previously demonstrated that although hyperthyroid rats presented leptin effects on TSH secretion, those effects were abolished in hypothyroid rats. We addressed the hypothesis that changes in the STAT3 pathway might explain the lack of TSH response to leptin in hypothyroidism by evaluating the protein content of components of leptin signalling via the STAT3 pathway in the hypothalamus and pituitary of hypothyroid (0·03% methimazole in the drinking water/21 days) and hyperthyroid (thyroxine 5 μg/100 g body weight /5 days) rats.

Minireview: The neural regulation of the hypothalamic-pituitary-thyroid axis.

Thyroid hormone (TH) signaling plays an important role in development and adult life. Many organisms may have evolved under selective pressure of exogenous TH, suggesting that thyroid hormone signaling is phylogenetically older than the systems that regulate their synthesis. Therefore, the negative feedback system by TH itself was probably the first mechanism of regulation of circulating TH levels.

Central NPY-Y5 receptors activation plays a major role in fasting-induced pituitary-thyroid axis suppression in adult rat.

Neuropeptide Y (NPY) inhibits TRH neurons in fed state, and hypothalamic NPY higher expression during fasting has been proposed to be involved in fasting-induced suppression of the hypothalamus-pituitary-thyroid (HPT) axis. We investigated the role of central Y5 receptors in the control of thyrotropin (TSH) and thyroid hormone (TH) secretion. Fed and fasting rats received twice daily central injections (3rd ventricle) of Y5 receptor antagonist (CGP71683; 15nmol/rat) for 72h.

Acute effects of endocannabinoid anandamide and CB1 receptor antagonist, AM251 in the regulation of thyrotropin secretion.

We examined the acute effects of endocannabinoid, anandamide, and of synthetic cannabinoid receptor antagonist, AM251[N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide], on TSH, thyroxine (T(4)), and triiodothyronine (T(3)) secretions. Euthyroid male rats showed a 42% decrease in serum TSH, 2 h after a single i.p.

Time course of echocardiographic and electrocardiographic parameters in myocardial infarct in rats.

In animal models the evaluation of myocardial infarct size in vivo and its relation to the actual lesion found post mortem is still a challenge. The purpose of the current study was to address if the conventional electrocardiogram (ECG) and/or echocardiogram (ECHO) could be used to adequately predict the size of the infarct in rats. Wistar rats were infarcted by left coronary ligation and then ECG, ECHO and histopathology were performed at 1, 7 and 28 days after surgery.

Thyroid function disturbance and type 3 iodothyronine deiodinase induction after myocardial infarction in rats a time course study.

In humans, there is a significant decrease in serum T(3) and increase in rT(3) at different time points after myocardial infarction, whereas serum TSH and T(4) remain unaltered. We report here a time course study of pituitary-thyroid function and thyroid hormone metabolism in rats subjected to myocardial infarction by left coronary ligation (INF). INF- and sham-operated animals were followed by serial deiodination assays and thyroid function tests, just before, and 1, 4, 8, and 12 wk after surgery.

Role of renin-angiotensin system in development of heart failure induced by myocardial infarction in rats.

We investigated the morphologic and functional changes of infarcted rat hearts under a paradigm of angiotensinconverting enzyme inhibition. Myocardial infarction was induced by left coronary artery ligation and a control group (SHAM) underwent sham-operation. Infarcted rats received normal drinking water with (CAP group) or without (INF group) captopril.

Sertraline, a selective serotonin reuptake inhibitor, affects thirst, salt appetite and plasma levels of oxytocin and vasopressin in rats.

We investigated the effects of chronic administration of sertraline (SERT; approximately 20 mg kg(-1) day(-1) in drinking water), a selective serotonin reuptake inhibitor, on water and sodium intake and on plasma levels of oxytocin (OT) and vasopressin (AVP) in basal and stimulated conditions. Basal water intake was reduced in SERT-treated rats. After 24 h of water deprivation, rats treated with SERT for 21 days ingested less water than the control rats (9.

Cellular cardiomyoplasty in large myocardial infarction: can the beneficial effect be enhanced by ACE-inhibitor therapy?

Background: Cellular cardiomyoplasty with bone marrow derived stromal (MSC) and mononuclear (BMNC) cells has been shown to improve performance of infarcted hearts. We performed a comparative study with MSC and BMNC and tested the hypothesis that captopril treatment could enhance the beneficial effect of cell therapy in large myocardial infarctions.

Methods: Male syngeneic Wistar rats underwent experimental infarction and were randomized to receive 1-3 x 10(6) MSC, 10(8) BMNC or vehicle (BSS group).

Ectopic ossification in the scar tissue of rats with myocardial infarction.

We describe the occurrence of bone-like formations in the left ventricular wall of infarcted rats treated or not with bone marrow cells injected systemically or locally into the myocardium. The incidence of ectopic calcification in hearts has been reported in rare cases in children with infarcts without previous coronary artery disease. Recently, ventricular calcification has been correlated with unselected bone marrow cell transplantation into infarcted rat hearts.

G-CSF does not improve systolic function in a rat model of acute myocardial infarction.

Objective: Granulocyte colony-stimulating factor (G-CSF) has been reported to improve cardiac performance by increasing the number of bone marrow stem cell in the peripheral circulation. The aim of this study was to investigate the impact of G-CSF administration on cardiac function in a rat model of acute myocardial infarction.

Methods: Recombinant human G-CSF (Filgrastim, 100 microg/kg, sc) twice a day during seven consecutive days (G-CSF group, n=13) or vehicle (control group, n=10) was administrated three hours after left anterior coronary artery ligation.

Ectopic Ossification in the Scar Tissue of Rats with Myocardial Infarction.

We describe the occurrence of bone-like formations in the left ventricular wall of infarcted rats treated or not with bone marrow cells injected systemically or locally into the myocardium. The incidence of ectopic calcification in hearts has been reported in rare cases in children with infarcts without previous coronary artery disease. Recently, ventricular calcification has been correlated with unselected bone marrow cell transplantation into infarcted rat hearts.

Cardiac autonomic dysfunction in rats chronically treated with anabolic steroid.

To date no published data exist regarding the effects of chronic high-dose anabolic-androgenic steroid administration on tonic cardiac autonomic control. The aim of this study was to evaluate, by power spectral analysis of heart rate variability (HRV), the effects of chronic treatment with supraphysiological doses of nandrolone decanoate (DECA) on tonic cardiac autonomic regulation in sedentary rats. Male Wistar rats were treated weekly with 10 mg kg(-1) of DECA (n=7) or vehicle (CONTROL, n=7) for 10 weeks.

A reassessment of the role of serotonergic system in the control of feeding behavior.

The role of serotonergic system in the feeding behavior was appraised by electrolytic lesions in the dorsal raphe nucleus (DRN) and administration of para-chlorophenylalanine (PCPA, 3 mg/5 microl, icv). Chronic evaluations were accomplished through 120 and 360 days in PCPA-injected and DRN-lesioned rats, respectively. Acute food intake was evaluated in fasted rats and submitted to injection of PCPA and hydroxytryptophan (LHTP, 30 mg/kg, ip).

Dipsogenic stimulation in ibotenic DRN-lesioned rats induces concomitant sodium appetite.

The main purpose of this study was to investigate whether dipsogenic stimuli influences the sodium appetite of rats with ibotenic acid lesion of the dorsal raphe nucleus (IBO-DRN). Compared to control, rats microinjected with phosphate buffer (PB-DRN), the ingestion of 0.3M NaCl was enhanced in IBO-DRN at 21 and 35 days after DRN lesion under a protocol of fluids and food deprivation.

Brain serotonin depletion enhances the sodium appetite induced by sodium depletion or beta-adrenergic stimulation.

We investigate the influence of brain serotonin depletion on the sodium appetite. Rats depleted of serotonin through the systemic administration of p-chlorophenylalanine (300 mg/kg, ip, for 2 days) showed an intense natriorexigenic response induced by sodium depletion (furosemide, 20 mg/kg, sc, 24 h before water and 1.8% NaCl presentation).