scholarly journals Metabolism of thyroid hormones in cultured cardiac fibroblasts of neonatal rats

2002 ◽  
Vol 174 (1) ◽  
pp. 111-119 ◽  
Author(s):  
SM van der Heide ◽  
TJ Visser ◽  
ME Everts ◽  
PH Klaren
Keyword(s):  
Thyroid Hormones ◽  
Time Course ◽  
Cardiac Fibroblasts ◽  
Heart Tissue ◽  
Water Soluble ◽  
Neonatal Rat ◽  
Uridine Diphosphate ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism

We have investigated the potential role of fibroblasts in local thyroid hormone metabolism in neonatal rat heart. Incubation of cardiac fibroblasts with thyroxine (T4) or 3,5,3'-tri-iodothyronine (T3) resulted in the appearance of water-soluble metabolites, whereas incubation of cardiomyocytes under the same conditions did not or did so to a much lesser extent. Time-course studies showed that production is already evident after 1-5 h of exposure and that the process equilibrates after 24-48 h. Analysis of the products revealed both the T4 and the T3 metabolites to be glucuronides. These results were corroborated by the detection of uridine diphosphate (UDP)-glucuronyltransferase activity in cardiac fibroblasts. We found no indication for outer ring deiodination in fibroblasts, cardiomyocytes or heart homogenates. From these results we have concluded that cardiac fibroblasts, but not cardiomyocytes, are able to glucuronidate T4 and T3 and secrete the conjugates. This could play a role in local metabolism, e.g. to protect the heart tissue from high levels of thyroid hormones.

Neutralization of TNF does not influence endotoxininduced changes in thyroid hormone metabolism in humans

1999 ◽  
Vol 276 (2) ◽  
pp. R357-R362 ◽  
Author(s):  
Tom van der Poll ◽  
Erik Endert ◽  
Susette M. Coyle ◽  
Jan M. Agosti ◽  
Stephen F. Lowry
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Stimulating Hormone ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism ◽  
Healthy Humans ◽  
Transient Rise ◽  
Induced Changes ◽  
Necrosis Factor ◽  
Control Study

To determine the role of tumor necrosis factor (TNF) in endotoxin-induced changes in plasma thyroid hormone and thyroid-stimulating hormone (TSH) concentrations, 24 healthy postabsorptive humans were studied on a control study day ( n= 6), after infusion of a recombinant TNF receptor IgG fusion protein (TNFR:Fc; 6 mg/m2; n = 6) after intravenous injection of endotoxin (2 ng/kg; n = 6), or after administration of endotoxin with TNFR:Fc ( n = 6). Administration of TNFR:Fc alone did not affect thyroid hormone or TSH levels when compared with the control day. Endotoxin induced a transient rise in plasma TNF activity (1.5 h: 219 ± 42 pg/ml), which was completely prevented by TNFR:Fc ( P < 0.05). After endotoxin administration, plasmal-thyroxine (T4), free T4, 3,5,3′-triiodothyronine (T3), and TSH were lower and 3,3′,5′-triiodothyronine was higher than on the control day (all P < 0.05). Coinfusion of TNFR:Fc with endotoxin did not influence these endotoxin-induced changes. Our results suggest that endogenous TNF does not play an important role in the alterations in plasma thyroid hormone and TSH concentrations induced by mild endotoxemia in healthy humans.

The role of cardiac fibroblasts in post-myocardial heart tissue repair

2016 ◽  
Vol 101 (2) ◽  
pp. 231-240 ◽  
Author(s):  
Dimitry A. Chistiakov ◽  
Alexander N. Orekhov ◽  
Yuri V. Bobryshev
Keyword(s):  
Tissue Repair ◽  
Cardiac Fibroblasts ◽  
Heart Tissue

The role of selenium in thyroid hormone metabolism

1991 ◽  
Vol 69 (11) ◽  
pp. 1648-1652 ◽  
Author(s):  
John R. Arthur
Keyword(s):  
Thyroid Hormone ◽  
Iodine Deficiency ◽  
Selenium Deficiency ◽  
Major Influence ◽  
Type I ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism ◽  
Iodothyronine Deiodinases ◽  
Clinical Changes

In animals, decreases in selenium-containing glutathione peroxidase activity and the resultant impairment of peroxide metabolism can account for many, but not all of the biochemical and clinical changes caused by selenium deficiency. Recently, however, type I iodothyronine 5′-deiodinase has also been shown to be a selenium-containing enzyme. This explains the impairment of thyroid hormone metabolism caused by selenium deficiency in animals with a normal vitamin E status. Since iodothyronine 5′-deiodinases are essential for the production of the active thyroid hormone 3,5,3′-triiodothyronine, some of the consequences of selenium deficiency may result from thyroid changes rather than inability to metabolise peroxides. In particular, the impaired thyroid hormone metabolism may be responsible for decreased growth and resistance to cold stress in selenium-deficient animals. A further consequence of the role of selenium in thyroid hormone metabolism is the exacerbation of some of the thyroid changes in iodine deficiency by a concurrent selenium deficiency. Selenium status may therefore have a major influence on the outcome of iodine deficiency in both human and animal populations.Key words: selenium, thyroid hormones, iodothyronine deiodinases, iodine, nutritional disorders.

scholarly journals Actin dynamics is rapidly regulated by the PTEN and PIP2 signaling pathways leading to myocyte hypertrophy

2014 ◽  
Vol 307 (11) ◽  
pp. H1618-H1625 ◽  
Author(s):  
Jieli Li ◽  
Elaine J. Tanhehco ◽  
Brenda Russell
Keyword(s):  
Time Course ◽  
Ventricular Myocytes ◽  
Initial Step ◽  
Heart Tissue ◽  
Neonatal Rat ◽  
Actin Dynamics ◽  
Mouse Heart ◽  
Dependent Manner ◽  
Ang Ii ◽  
Myocyte Hypertrophy

Mature cardiac myocytes are terminally differentiated, and the heart has limited capacity to replace lost myocytes. Thus adaptation of myocyte size plays an important role in the determination of cardiac function. The hypothesis tested is that regulation of the dynamic exchange of actin leads to cardiac hypertrophy. ANG II was used as a hypertrophic stimulant in mouse heart and neonatal rat ventricular myocytes (NRVMs) in culture for assessment of a mechanism for regulation of actin dynamics by phosphatidylinositol 4,5-bisphosphate (PIP2). Actin dynamics in NRVMs rapidly increased in a PIP2-dependent manner, measured by imaging and fluorescence recovery after photobleaching (FRAP). A significant increase in PIP2 levels was found by immunoblotting in both adult mouse heart tissue and cultured NRVMs. Inhibition of phosphatase and tensin homolog (PTEN) in NRVMs markedly blunted ANG II-induced increases in actin dynamics, the PIP2 level, and cell size. Furthermore, PTEN activity was dramatically upregulated in ANG II-treated NRVMs but downregulated when PTEN inhibitors were used. The time course of the rise in the PIP2 level was inversely related to the fall in the PIP3 level, which was significant by 30 min in ANG II-treated NRVMs. However, significant translocation of PTEN to the plasma membrane occurred by 10 min, suggesting a crucial initial step for PTEN for the cellular responses to ANG II. In conclusion, PTEN and PIP2 signaling may play an important role in myocyte hypertrophy by the regulation of actin filament dynamics, which is induced by ANG II stimulation.

scholarly journals Lacking thyroid hormone receptor β gene does not influence alterations in peripheral thyroid hormone metabolism during acute illness

2008 ◽  
Vol 197 (1) ◽  
pp. 151-158 ◽  
Author(s):  
J Kwakkel ◽  
O Chassande ◽  
H C van Beeren ◽  
W M Wiersinga ◽  
A Boelen
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism ◽  
Males And Females ◽  
Induced Changes ◽  
Thyroid Hormone Receptor Β

The downregulation of liver deiodinase type 1 (D1) is supposed to be one of the mechanisms behind the decrease in serum tri-iodothyronine (T3) observed during non-thyroidal illness (NTI). Liver D1 mRNA expression is positively regulated by T3, mainly via the thyroid hormone receptor (TR)β1. One might thus expect that lacking the TRβ gene would result in diminished downregulation of liver D1 expression and a smaller decrease in serum T3 during illness. In this study, we used TRβ−/− mice to evaluate the role of TRβ in lipopolysaccharide (LPS, a bacterial endotoxin)-induced changes in thyroid hormone metabolism. Our results show that the LPS-induced serum T3 and thyroxine and liver D1 decrease takes place despite the absence of TRβ. Furthermore, we observed basal differences in liver D1 mRNA and activity between TRβ−/− and wild-type mice and TRβ−/− males and females, which did not result in differences in serum T3. Serum T3 decreased rapidly after LPS administration, followed by decreased liver D1, indicating that the contribution of liver D1 during NTI may be limited with respect to decreased serum T3 levels. Muscle D2 mRNA did not compensate for the low basal liver D1 observed in TRβ−/− mice and increased in response to LPS in TRβ−/− and WT mice. Other (TRβ independent) mechanisms like decreased thyroidal secretion and decreased binding to thyroid hormone-binding proteins probably play a role in the early decrease in serum T3 observed in this study.

Abstract 220: miR-486 Mediates the Benefits of Exercise in Attenuating Cardiac Fibrosis

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Dongchao Lv ◽  
Yihua Bei ◽  
Qiulian Zhou ◽  
Qi Sun ◽  
Tianzhao Xu ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Mrna Level ◽  
Neonatal Rat ◽  
Cardiac Growth ◽  
Non Coding Rnas ◽  
Exercise Induced ◽  
Proliferation Assays

MicroRNAs (miRNAs, miRs), a novel group of small non-coding RNAs, play important roles in cardiac fibrosis. Exercise-induced physiological cardiac growth is associated with hypertrophy and proliferation of cardiomyocytes. In addition, exercise has been shown to inhibit cardiac fibrosis. However, relative little is known about whether exercise could attenuating cardiac fibrosis via targeting miRNA. miR-486 is a muscle enriched miRNAs, however, its role in heart is relative unclear. The current study aimed to investigate the role of miR-486 in exercise-induced cardiac growth in a 3-week swimming training murine model as well as in the function of cardiac fibroblasts and production of extracellular matrix (ECM) using neonatal rat cardiac fibroblasts in primary culture. Our data showed that exercised mice displayed increased about three-fold expression of miR-486 in hearts as measured by microarray analysis and qRT-PCRs. EdU proliferation assays demonstrated that miR-486 mimics decreased (5.90%±0.57% vs 4.02%±0.27% in nc-mimics vs miR-486-mimics, respectively), while miR-486 inhibitor increased the proliferation of cardiac fibroblasts in vitro (5.87%±0.16% vs 9.60%±0.58% in nc-inhibitor vs miR-486-inhibitor, respectively). Although downregulation of miR-486 had no regulatory effect on α-sma and collagen-1 gene expression in cardiac fibroblasts, overexpression of miR-486 significantly reduced the mRNA level of α-sma (1.01±0.08 vs 0.28±0.04 in nc-mimics vs miR-486-mimics, respectively) and collagen-1(1.02±0.12 vs 0.58±0.09 in nc-mimics vs miR-486-mimics, respectively), indicative of attenuated activation of fibroblasts and reduced production of ECM. These data reveal that miR-486 is essentially involved in the proliferation and activation of cardiac fibroblasts, and might be a key regulator mediating the benefit of exercise in preventing cardiac fibrosis.

Abstract 250: Elucidating the Role of Platelet Derived Growth Factor Receptor Alpha Signaling in Cardiac Fibroblasts

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Malina J Ivey ◽  
Michelle Tallquist
Keyword(s):  
Preliminary Data ◽  
Time Course ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Cardiac Fibroblast ◽  
Proliferating Cells ◽  
Time Course Experiment

Cardiac fibrosis is a major component of heart disease and is a hallmark of decreased cardiac function. Currently, there are no treatments that attenuate fibrosis directly. This major hurdle can be overcome by targeting the resident fibroblast. Preliminary data demonstrates that loss of PDGFRα expression in the adult cardiac fibroblast lineage results in loss of over half of resident fibroblasts. A time course experiment revealed that in as little as 4 days after PDGFRα gene deletion fibroblast loss can observed. Based on the basal level of fibroblast proliferation (0.8%+/-0.9, i.e. 4 of 398 cells), we hypothesize that PDGFRα signaling is essential for fibroblast maintenance and that fibroblasts undergo rapid turnover. We have begun to elucidate which downstream signals of PDGFRα are involved the different roles of the fibroblast. Using a PDGFRα-dependent-PI3K-deficient mouse model, preliminary data indicates that PDGFRα-dependent PI3K signaling is involved in this cell survival response. Future studies will investigate cardiac fibroblast maintenance signals by determining which cell types secrete PDGF ligands. We will also investigate the role of PDGFRα signaling after myocardial infarction. Our lab has genetic tools that enable us to follow fibroblasts after injury, and we have determined both the number of proliferating fibroblasts at different time points, as well as the fraction of fibroblasts that make up the total population of proliferating cells after LAD ligation. Our preliminary data in control hearts shows that fibroblasts reach their peak of proliferation within a week after infarction, although they remain one of the most proliferative cell types as long as three weeks after induction. Our studies will illuminate the role of the fibroblast in tissue homeostasis and after infarction and identify how these cells contribute to overall cardiovascular function and delineate the fine balance between the essential and detrimental functions of the fibroblast.

The role of dietary fat in peripheral thyroid hormone metabolism

Metabolism ◽  
1980 ◽  
Vol 29 (10) ◽  
pp. 930-935 ◽  
Author(s):  
M.H. Otten ◽  
G. Hennemann ◽  
R. Docter ◽  
T.J. Visser
Keyword(s):  
Thyroid Hormone ◽  
Dietary Fat ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism

Meal-induced brown fat thermogenesis and thyroid hormone metabolism in rats

1985 ◽  
Vol 249 (5) ◽  
pp. E519-E524 ◽  
Author(s):  
Z. Glick ◽  
S. Y. Wu ◽  
J. Lupien ◽  
R. Reggio ◽  
G. A. Bray ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Serum Concentrations ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism ◽  
Low Protein ◽  
Bat Mitochondria ◽  
Brown Adipose ◽  
Serum T3 ◽  
The Relationship

The relationship between the meal-induced increase in brown adipose tissue (BAT) thermogenesis, determined by the level of GDP binding to BAT mitochondria, and thyroid hormone metabolism have been examined. A single low-protein, high-carbohydrate meal resulted in a significant increase in the thermogenic activity of BAT. This effect on BAT thermogenesis was accompanied by significant increases in activity of thyroxine 5'-monodeiodinase in the BAT (P less than 0.05) and liver (P less than 0.02) but not with any significant changes in serum concentrations of the thyroid hormones. The stimulatory effects of the meal on BAT thermogenesis and hepatic thyroxine (T4) to triiodothyronine (T3) conversion persisted at least as late as 24 h after meal onset. Food deprivation for 40 h was associated with large reductions in serum concentrations of T3 (P less than 0.01) and T4 (P less than 0.001), but deprivation for 18 h had no significant effect on serum T3 and T4 concentrations. Our data indicate that the meal-induced increase in BAT thermogenesis can be independent from changes in serum concentrations of thyroid hormones and suggest that T3 produced in BAT in response to feeding may play a role in the thermic response of this tissue to meals.

THE ROLE OF THYRONINE IN THYROID HORMONE METABOLISM

1979 ◽  
Vol 49 (4) ◽  
pp. 658-660 ◽  
Author(s):  
P. WILLETTS ◽  
D.N. CROSSLEY ◽  
D.B. RAMSDEN ◽  
R. HOFFENBERG
Keyword(s):  
Thyroid Hormone ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism
Sign in / Sign up

Export Citation Format

Share Document