scholarly journals Chronic local inflammation in mice results in decreased TRH and type 3 deiodinase mRNA expression in the hypothalamic paraventricular nucleus independently of diminished food intake

2006 ◽  
Vol 191 (3) ◽  
pp. 707-714 ◽  
Author(s):  
A Boelen ◽  
J Kwakkel ◽  
W M Wiersinga ◽  
E Fliers
Keyword(s):  
Thyroid Hormone ◽  
Food Intake ◽  
Mrna Expression ◽  
Chronic Inflammation ◽  
Paraventricular Nucleus ◽  
Local Inflammation ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism ◽  
Pituitary Thyroid Axis ◽  
Hpt Axis

During illness, changes in thyroid hormone metabolism occur, known as nonthyroidal illness and characterised by decreased serum triiodothyronine (T3) and thyroxine (T4) without an increase in TSH. A mouse model of chronic illness is local inflammation, induced by a turpentine injection in each hind limb. Although serum T3 and T4 are markedly decreased in this model, it is unknown whether turpentine administration affects the central part of the hypothalamus–pituitary–thyroid axis (HPT-axis). We therefore studied thyroid hormone metabolism in hypothalamus and pituitary of mice during chronic inflammation induced by turpentine injection. Using pair-fed controls, we could differentiate between the effects of chronic inflammation per se and the effects of restricted food intake as a result of illness. Chronic inflammation increased interleukin (IL)-1β mRNA expression in the hypothalamus more rapidly than in the pituitary. This hypothalamic cytokine response was associated with a rapid increase in local D2 mRNA expression. By contrast, no changes were present in pituitary D2 expression. TSHβ mRNA expression was altered compared with controls. Comparing chronic inflamed mice with pair-fed controls, both preproTSH releasing hormone (TRH) and D3 mRNA expression in the paraventricular nucleus were significantly lower 48 h after turpentine administration. The timecourse of TSHβ mRNA expression was completely different in inflamed mice compared with pair-fed mice. Turpentine administration resulted in significantly decreased TSHβ mRNA expression only after 24 h while later in time it was lower in pair-fed controls. In conclusion, central thyroid hormone metabolism is altered during chronic inflammation and this cannot solely be attributed to diminished food intake.

scholarly journals Simultaneous changes in central and peripheral components of the hypothalamus-pituitary-thyroid axis in lipopolysaccharide-induced acute illness in mice

2004 ◽  
Vol 182 (2) ◽  
pp. 315-323 ◽  
Author(s):  
A Boelen ◽  
J Kwakkel ◽  
DC Thijssen-Timmer ◽  
A Alkemade ◽  
E Fliers ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Time Course ◽  
Acute Illness ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Hpt Axis

During illness, major changes in thyroid hormone metabolism and regulation occur; these are collectively known as non-thyroidal illness and are characterized by decreased serum triiodothyronine (T(3)) and thyroxine (T(4)) without an increase in serum TSH. Whether alterations in the central part of the hypothalamus-pituitary-thyroid (HPT) axis precede changes in peripheral thyroid hormone metabolism instead of vice versa, or occur simultaneously, is presently unknown. We therefore studied the time-course of changes in thyroid hormone metabolism in the HPT axis of mice during acute illness induced by bacterial endotoxin (lipopolysaccharide; LPS).LPS rapidly induced interleukin-1beta mRNA expression in the hypothalamus, pituitary, thyroid and liver. This was followed by almost simultaneous changes in the pituitary (decreased expression of thyroid receptor (TR)-beta2, TSHbeta and 5'-deiodinase (D1) mRNAs), the thyroid (decreased TSH receptor mRNA) and the liver (decreased TRbeta1 and D1 mRNA). In the hypothalamus, type 2 deiodinase mRNA expression was strongly increased whereas preproTRH mRNA expression did not change after LPS. Serum T(3) and T(4) fell only after 24 h.Our results suggested almost simultaneous involvement of the whole HPT axis in the downregulation of thyroid hormone metabolism during acute illness.

scholarly journals Neuropeptide Y1 and Y5 Receptors Mediate the Effects of Neuropeptide Y on the Hypothalamic-Pituitary-Thyroid Axis

Endocrinology ◽  
2002 ◽  
Vol 143 (12) ◽  
pp. 4513-4519 ◽  
Author(s):  
Csaba Fekete ◽  
Sumit Sarkar ◽  
William M. Rand ◽  
John W. Harney ◽  
Charles H. Emerson ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Food Intake ◽  
Neuropeptide Y ◽  
Paraventricular Nucleus ◽  
Receptor Agonist ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Ad Libitum ◽  
Thyroid Hormone Levels ◽  
Hpt Axis

Abstract Neuropeptide Y (NPY) is one of the most important hypothalamic-derived neuropeptides mediating the effects of leptin on energy homeostasis. Central administration of NPY not only markedly stimulates food intake, but simultaneously inhibits the hypothalamic-pituitary-thyroid axis (HPT axis), replicating the central hypothyroid state associated with fasting. To identify the specific NPY receptor subtypes involved in the action of NPY on the HPT axis, we studied the effects of the highly selective Y1 ([Phe7,Pro34]pNPY) and Y5 ([chicken pancreatic polypeptide1–7, NPY19–23, Ala31, Aib32 (aminoisobutyric acid), Q34]human pancreatic polypeptide) receptor agonists on circulating thyroid hormone levels and proTRH mRNA in hypophysiotropic neurons of the hypothalamic paraventricular nucleus. The peptides were administered continuously by osmotic minipump into the cerebrospinal fluid (CSF) over 3 d in ad libitum-fed animals and animals pair-fed to artificial CSF (aCSF)-infused controls. Both Y1 and Y5 receptor agonists nearly doubled food intake compared with that of control animals receiving aCSF, similar to the effect observed for NPY. NPY, Y1, and Y5 receptor agonist administration suppressed circulating levels of thyroid hormones (T3 and T4) and resulted in inappropriately normal or low TSH levels. These alterations were also associated with significant suppression of proTRH mRNA in the paraventricular nucleus, particularly in the Y1 receptor agonist-infused group [aCSF, NPY, Y1, and Y5 (density units ± sem), 97.2 ± 8.6, 39.6 ± 8.4, 19.9 ± 1.9, and 44.6 ± 8.4]. No significant differences in thyroid hormone levels, TSH, or proTRH mRNA were observed between the agonist-infused FSanimals eating ad libitum and the agonist-infused animals pair-fed with vehicle-treated controls. These data confirm the importance of both Y1 and Y5 receptors in the NPY-mediated increase in food consumption and demonstrate that both Y1 and Y5 receptors can mediate the inhibitory effects of NPY on the HPT axis.

scholarly journals Progesterone regulates hypothalamic-pituitary-thyroid axis

2017 ◽  
Author(s):  
Chunyun Zhong ◽  
Kewen Xiong ◽  
Xin Wang
Keyword(s):  
Thyroid Hormone ◽  
Aquatic Ecosystems ◽  
Endocrine System ◽  
Hormone Metabolism ◽  
Hormone Synthesis ◽  
Thyroid Hormone Metabolism ◽  
Expression Of Genes ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Hpt Axis

AbstractProgesterone is a natural steroid hormone excreted by animals and humans, which has been frequently detected in the aquatic ecosystems. The effects of the residual progesterone on fish are unclear. In this study, we aimed to examine the effects of progesterone on the hypothalamic-pituitary-thyroid (HPT) axis by detecting the gene transcriptional expression levels. Zebrafish embryos were treated with different concentrations of progesterone from 12 hours post-fertilization (hpf) to 120 hpf. Total mRNA was extracted and the transcriptional profiles of genes involved in HPT axis were examined using qPCR. The genes related to thyroid hormone metabolism and thyroid hormone synthesis were up-regulated in zebrafish exposed to progesterone. These results indicated that progesterone affected the mRNA expression of genes involved in the HPT axis, which might interrupt the endocrine system in zebrafish. Our data also suggested that zebrafish is a useful tool for evaluating the effects of chemicals on the thyroid endocrine system.

scholarly journals Differential effects of leptin and refeeding on the fasting-induced decrease of pituitary type 2 deiodinase and thyroid hormone receptor β2 mRNA expression in mice

2006 ◽  
Vol 190 (2) ◽  
pp. 537-544 ◽  
Author(s):  
A Boelen ◽  
J Kwakkel ◽  
X G Vos ◽  
W M Wiersinga ◽  
E Fliers
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Hormone Metabolism ◽  
Serum Leptin ◽  
Thyroid Hormone Metabolism ◽  
Hpt Axis ◽  
As Effects

Profound changes in thyroid hormone metabolism occur in the central part of the hypothalamus–pituitary–thyroid (HPT) axis during fasting. Hypothalamic changes are partly reversed by leptin administration, which decreases during fasting. It is unknown to what extent leptin affects the HPT axis at the level of the pituitary. We, therefore, studied fasting-induced alterations in pituitary thyroid hormone metabolism, as well as effects of leptin administration on these changes. Because refeeding rapidly increased serum leptin, the same parameters were studied after fasting followed by refeeding. Fasting for 24 h decreased serum T3 and T4 and pituitary TSHβ, type 2deiodinase (D2), and thyroid hormone receptor β2 (TRβ2) mRNA expression. The decrease in D2 and TRβ2 mRNA expression was prevented when 20 μg leptin was administered twice during fasting. By contrast, the decrease in TSHβ mRNA expression was unaffected. A single dose of leptin given after 24 h fasting did not affect decreased TSHβ, D2, and TRβ2 mRNA expression, while 4 h refeeding resulted in pituitary D2 and TRβ2 mRNA expression as observed in control mice. Serum leptin, T3, and T4 after refeeding were similar compared with leptin administration. We conclude that fasting decreases pituitary TSHβ, D2, and TRβ2 mRNA expression, which (with the exception of TSHβ) can be prevented by leptin administration during fasting. Following 24 h fasting, 4 h refeeding completely restores pituitary D2 and TRβ2 mRNA expression, while a single leptin dose is ineffective. This indicates that other postingestion signals may be necessary to modulate rapidly the fasting-induced decrease in pituitary D2 and TRβ2 mRNA expression.

scholarly journals Interleukin-18, a proinflammatory cytokine, contributes to the pathogenesis of non-thyroidal illness mainly via the central part of the hypothalamus-pituitary-thyroid axis

2004 ◽  
pp. 497-502 ◽  
Author(s):  
A Boelen ◽  
J Kwakkel ◽  
M Platvoet-ter Schiphorst ◽  
B Mentrup ◽  
A Baur ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Proinflammatory Cytokine ◽  
Biological Properties ◽  
Thyroid Hormone Metabolism ◽  
Pituitary Thyroid Axis ◽  
Serum T3 ◽  
Thyroid Axis ◽  
Hpt Axis

OBJECTIVE: Proinflammatory cytokines are involved in the pathogenesis of non-thyroidal illness (NTI), as shown by studies with IL-6-/- and IL-12-/- mice. Interleukin (IL)-6 changes peripheral thyroid hormone metabolism, and IL-12 seems to be involved in the regulation of the central part of the hypothalamic-pituitary-thyroid (HPT) axis during illness. IL-18 is a proinflammatory cytokine which shares important biological properties with IL-12, such as interferon (IFN)-gamma-inducing activity. DESIGN: By studying the changes in the HPT-axis during bacterial lipopolysaccharide (LPS)-induced illness in IL-18-/-, IFNgammaR-/- and wild-type (WT) mice, we wanted to unravel the putative role of IL-18 and IFNgamma in the pathogenesis of NTI. RESULTS: LPS induced a decrease in pituitary type 1 deiodinase (D1) activity (P<0.05, ANOVA) in WT mice, but not in IL-18-/- mice, while the decrease in D2 activity was similar in both strains. LPS decreased serum thyroid hormone levels and liver D1 mRNA within 24 h similarly in IL-18-/-, and WT mice. The expression of IL-1, IL-6 and IFNgamma mRNA expression was significantly lower in IL-18-/- mice than in WT, while IL-12 mRNA expression was similar. IFNgammaR-/- mice had higher basal D1 activity in the pituitary than WT mice (P<0.05); LPS induced a decrease of D2, but not of D1, activity in the pituitary which was similar in both strains. In the liver, the LPS-induced increase in cytokine expression was not different between IFNgammaR-/- mice and WT mice, and the decrease in serum T3 and T4 levels and hepatic D1 mRNA was also similar. CONCLUSIONS: The relative decrease in serum T3 and T4 and liver D1 mRNA in response to LPS is similar in IL-18-/-, IFNgammaR-/- and WT mice despite significant changes in hepatic cytokine induction. However, the LPS-induced decrease in D1 activity in the pituitary of WT mice is absent in IL-18-/- mice; in contrast, LPS did not decrease pituitary D1 activity in the IFNgammaR-/- mice or their WT, which might be due to the genetic background of the mice. Our results suggest that IL-18 is also involved in the regulation of the central part of the HPT axis during illness.

scholarly journals Tissue thyroid hormone metabolism is differentially regulated during illness in mice

2017 ◽  
Vol 233 (1) ◽  
pp. 25-36 ◽  
Author(s):  
Anita Boelen ◽  
Anne H van der Spek ◽  
Flavia Bloise ◽  
Emmely M de Vries ◽  
Olga V Surovtseva ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Target Genes ◽  
Severity Of Illness ◽  
Severe Pneumonia ◽  
Complex Nature ◽  
Local Inflammation ◽  
Hormone Metabolism ◽  
Nonthyroidal Illness ◽  
Thyroid Hormone Metabolism ◽  
Organ Specific

Illness induces major modifications in central and peripheral thyroid hormone (TH) metabolism, so-called nonthyroidal illness syndrome (NTIS). As a result, organ-specific changes in local TH availability occur depending on the type and severity of illness. Local TH availability is of importance for the regulation of the tissue-specific TH target genes and determined by the interplay between deiodinating enzymes, TH transport and TH receptor (TR) expression. In the present study, we evaluated changes in TH transport, deiodination and TR expression, the resulting tissue TH concentrations and the expression of TH target genes in liver and muscle in three animal models of illness. We induced (1) acute systemic inflammation by intraperitoneal injection of bacterial endotoxin (LPS), (2) chronic local inflammation by a turpentine injection in the hind limb and (3) severe pneumonia and sepsis by intranasal inoculation with Streptococcus pneumoniae. We found that all aspects of peripheral TH metabolism are differentially regulated during illness, depending on the organ studied and severity of illness. In addition, tissue TH concentrations are not equally affected by the decrease in serum TH concentrations. For example, the decrease in muscle TH concentrations is less severe than the decrease observed in liver. In addition, despite lower TH concentrations in muscle in all three models, muscle T3 action is differentially affected. These observations help to understand the complex nature of the nonthyroidal illness syndrome.

Differential Effects of Sepsis and Chronic Inflammation on Diaphragm Muscle Fiber Type, Thyroid Hormone Metabolism, and Mitochondrial Function

Thyroid ◽  
2016 ◽  
Vol 26 (4) ◽  
pp. 600-609 ◽  
Author(s):  
Flavia F. Bloise ◽  
Anne H. van der Spek ◽  
Olga V. Surovtseva ◽  
Tania Maria Ortiga-Carvalho ◽  
Eric Fliers ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Chronic Inflammation ◽  
Muscle Fiber ◽  
Mitochondrial Function ◽  
Fiber Type ◽  
Muscle Fiber Type ◽  
Diaphragm Muscle ◽  
Hormone Metabolism ◽  
Differential Effects ◽  
Thyroid Hormone Metabolism

Thyrostimulin deficiency does not alter peripheral responses to acute inflammation-induced nonthyroidal illness

2014 ◽  
Vol 307 (6) ◽  
pp. E527-E537 ◽  
Author(s):  
Clementine J. J. van Zeijl ◽  
Olga V. Surovtseva ◽  
Joan Kwakkel ◽  
Hermina C. van Beeren ◽  
J. H. Duncan Bassett ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Acute Inflammation ◽  
Activity Levels ◽  
Hormone Metabolism ◽  
Glycoprotein Hormone ◽  
Nonthyroidal Illness ◽  
Thyroid Hormone Metabolism ◽  
Brown Adipose

Thyrostimulin, a putative glycoprotein hormone, comprises the subunits GPA2 and GPB5 and activates the TSH receptor (TSHR). The observation that proinflammatory cytokines stimulate GPB5 transcription suggested a role for thyrostimulin in the pathogenesis of nonthyroidal illness syndrome (NTIS). In the present study, we induced acute inflammation by LPS administration to GPB5−/− and WT mice to evaluate the role of thyrostimulin in peripheral thyroid hormone metabolism during NTIS. In addition to serum thyroid hormone concentrations, we studied mRNA expression and activity of deiodinase types I, II, and III (D1, D2, and D3) in peripheral T3 target tissues, including liver, muscle, and white and brown adipose tissue (WAT and BAT), of which the latter three express the TSHR. LPS decreased serum free (f)T4 and fT3 indexes to a similar extent in GPB5−/− and WT mice. Serum reverse (r)T3 did not change following LPS administration. LPS also induced significant alterations in tissue D1, D2, and D3 mRNA and activity levels, but only the LPS-induced increase in WAT D2 mRNA expression differed between GPB5−/− and WT mice. In conclusion, lacking GPB5 during acute illness does not affect the LPS-induced decrease of serum thyroid hormones while resulting in subtle changes in tissue D2 expression that are unlikely to be mediated via the TSHR.

scholarly journals Differential effects of fasting vs food restriction on liver thyroid hormone metabolism in male rats

2014 ◽  
Vol 224 (1) ◽  
pp. 25-35 ◽  
Author(s):  
E M de Vries ◽  
H C van Beeren ◽  
M T Ackermans ◽  
A Kalsbeek ◽  
E Fliers ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Food Intake ◽  
Caloric Restriction ◽  
Food Restriction ◽  
Male Rats ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism ◽  
Limited Food ◽  
Fasted Rats

A variety of illnesses that leads to profound changes in the hypothalamus–pituitary–thyroid (HPT) are axis collectively known as the nonthyroidal illness syndrome (NTIS). NTIS is characterized by decreased tri-iodothyronine (T3) and thyroxine (T4) and inappropriately low TSH serum concentrations, as well as altered hepatic thyroid hormone (TH) metabolism. Spontaneous caloric restriction often occurs during illness and may contribute to NTIS, but it is currently unknown to what extent. The role of diminished food intake is often studied using experimental fasting models, but partial food restriction might be a more physiologically relevant model. In this comparative study, we characterized hepatic TH metabolism in two models for caloric restriction: 36 h of complete fasting and 21 days of 50% food restriction. Both fasting and food restriction decreased serum T4concentration, while after 36-h fasting serum T3also decreased. Fasting decreased hepatic T3but not T4concentrations, while food restriction decreased both hepatic T3and T4concentrations. Fasting and food restriction both induced an upregulation of liver D3 expression and activity, D1 was not affected. A differential effect was seen inMct10mRNA expression, which was upregulated in the fasted rats but not in food-restricted rats. Other metabolic pathways of TH, such as sulfation and UDP-glucuronidation, were also differentially affected. The changes in hepatic TH concentrations were reflected by the expression of T3-responsive genesFasandSpot14only in the 36-h fasted rats. In conclusion, limited food intake induced marked changes in hepatic TH metabolism, which are likely to contribute to the changes observed during NTIS.

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