Interleukin 6 effects on the pituitary–thyroid axis in the rat

1994 ◽  
Vol 131 (3) ◽  
pp. 302-306 ◽  
Author(s):  
Luigi Bartalena ◽  
Lucia Grasso ◽  
Sandra Brogioni ◽  
Enio Martino
Keyword(s):  
Thyroid Hormone ◽  
Interleukin 6 ◽  
Saline Solution ◽  
Hormone Secretion ◽  
Neutralizing Antibody ◽  
Control Group ◽  
Apparent Lack ◽  
Tnf Α ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis

Bartalena L, Grasso L, Brogioni S, Martino E. Interleukin 6 effects on the pituitary–thyroid axis in the rat. Eur J Endocrinol 1994;131:302–6. ISSN 0804–4643 It has been postulated recently that cytokines, and in particular interleukin 1 (IL-1) and tumor necrosis factor-α TNF-α), may have a role in the pathogenesis of the changes of serum thyroid hormone concentrations that are encountered in patients with non-thyroidal illness (NTI). Many of the IL-1 and TNF-α effects are believed to be mediated by the induction of IL-6 synthesis, which might, therefore, represent an important mediator of thyroid hormone changes in NTI. To address this problem, male Wistar rats were injected subcutaneously with 2.5 μg of recombinant human IL-6 (rhIL-6, in 500 μl of saline solution), with 2.5 μg of rhIL-6 preincubated with 100 μl of anti-IL-6 neutralizing antibody or with saline solution alone (control group). Administration of rhIL-6 resulted in a significant decrease of thyroxine (T4) from 82 ± 4 nmol/l (mean± sem) to a nadir of 33 ± 3 nmol/l (p < 0.0001) after 48 h, and of triiodothyronine (T3) from 1.6 ± 0.1 to 0.8 ± 0.1 nmol/l after 48 h (p < 0.0001). A slight decrease in serum T4 and T3 concentrations also was observed in the control group, but the lowest values (T4, 66 ± 3 nmol/l; T3, 1.2 ± 0.1 nmol/l) were significantly higher (p < 0.0001) than in IL-6-treated rats. The IL-6-induced changes could be prevented by preincubation of rhIL-6 with its neutralizing antibody. Slight but not significant changes occurred in serum reverse T3 (rT3) concentration, so that the T4/rT3 ratio remained substantially unchanged after rhIL-6 injection, whereas the T4/T3 ratio decreased significantly from 53.6 to 39.9 (p < 0.02) in IL-6-treated rats. The effects of IL-6 on thyrotropin (TSH) were investigated after rendering the rats hypothyroid by methimazole administration for 3 weeks. Serum TSH decreased from 19.0 ± 6.8 to 13.3 ± 3.8 μg/l after 48 h (p < 0.01) in IL-6-treated rats, while it increased from 17.2 ± 2.8 to 25.8 ± 4.0 μg/l (p < 0.01) in the control group. These results show that a single injection of rhIL-6 causes a decrease in serum T4, T3 and TSH concentrations in the rat, without affecting serum rT3 levels. This is compatible with a predominantly central effect of the cytokine. The apparent lack of inhibition of 5′-deiodinating activity, a key feature of NTI, suggests that IL-6, if involved, is only one of the factors responsible for the changes of thyroid hormone secretion and metabolism observed in NTI. Luigi Bartalena, Istituto di Endocrinologia, University of Pisa, Viale del Tirreno 64, 56018 Tirrenia-Pisa, Italy

scholarly journals OctylPhenol (OP) Alone and in Combination with NonylPhenol (NP) Alters the Structure and the Function of Thyroid Gland of the Lizard Podarcis siculus

2021 ◽  
Vol 80 (3) ◽  
pp. 567-578 ◽  
Author(s):  
Rosaria Sciarrillo ◽  
Mariana Di Lorenzo ◽  
Salvatore Valiante ◽  
Luigi Rosati ◽  
Maria De Falco
Keyword(s):  
Thyroid Gland ◽  
Endocrine Disrupting Chemicals ◽  
Thyroid Stimulating Hormone ◽  
Control Group ◽  
Type Ii ◽  
Endocrine Disrupting ◽  
Pituitary Thyroid Axis ◽  
Podarcis Siculus ◽  
Thyroid Axis ◽  
By Products

Abstract Different environmental contaminants disturb the thyroid system at many levels. AlkylPhenols (APs), by-products of microbial degradation of AlkylPhenol Polyethoxylates (APEOs), constitute an important class of Endocrine Disrupting Chemicals (EDCs), the two most often used environmental APs being 4-nonylphenol (4-NP) and 4-tert-octylphenol (4-t-OP). The purpose of the present study was to investigate the effects on the thyroid gland of the bioindicator Podarcis siculus of OP alone and in combination with NP. We used radioimmunoassay to determine their effects on plasma 3,3′,5-triiodo-L-thyronine (T3), 3,3′,5,5′-L-thyroxine (T4), thyroid-stimulating hormone (TSH), and thyrotropin-releasing hormone (TRH) levels in adult male lizards. We also investigated the impacts of AP treatments on hepatic 5′ORD (type II) deiodinase and hepatic content of T3 and T4. After OP and OP + NP administration, TRH levels increased, whereas TSH, T3, and T4 levels decreased. Lizards treated with OP and OP + NP had a higher concentration of T3 in the liver and 5′ORD (type II) activity, whereas T4 concentrations were lower than that observed in the control group. Moreover, histological examination showed that the volume of the thyroid follicles became smaller in treated lizards suggesting that that thyroid follicular epithelial cells were not functionally active following treatment. This data collectively suggest a severe interference with hypothalamus–pituitary–thyroid axis and a systemic imbalance of thyroid hormones. Graphic Abstract

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 Selective TNF-α targeting with infliximab attenuates impaired oxygen metabolism and contractile function induced by an acute exposure to air particulate matter

2015 ◽  
Vol 309 (10) ◽  
pp. H1621-H1628 ◽  
Author(s):  
Timoteo Marchini ◽  
Verónica D'Annunzio ◽  
Mariela L. Paz ◽  
Lourdes Cáceres ◽  
Mariana Garcés ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Saline Solution ◽  
Contractile Function ◽  
Left Ventricular ◽  
Acute Exposure ◽  
Control Group ◽  
Contractile Reserve ◽  
Mice Model ◽  
Cardiovascular Morbidity And Mortality ◽  
Tnf Α

Inflammation plays a central role in the onset and progression of cardiovascular diseases associated with the exposure to air pollution particulate matter (PM). The aim of this work was to analyze the cardioprotective effect of selective TNF-α targeting with a blocking anti-TNF-α antibody (infliximab) in an in vivo mice model of acute exposure to residual oil fly ash (ROFA). Female Swiss mice received an intraperitoneal injection of infliximab (10 mg/kg body wt) or saline solution, and were intranasally instilled with a ROFA suspension (1 mg/kg body wt). Control animals were instilled with saline solution and handled in parallel. After 3 h, heart O2 consumption was assessed by high-resolution respirometry in left ventricle tissue cubes and isolated mitochondria, and ventricular contractile reserve and lusitropic reserve were evaluated according to the Langendorff technique. ROFA instillation induced a significant decrease in tissue O2 consumption and active mitochondrial respiration by 32 and 31%, respectively, compared with the control group. While ventricular contractile state and isovolumic relaxation were not altered in ROFA-exposed mice, impaired contractile reserve and lusitropic reserve were observed in this group. Infliximab pretreatment significantly attenuated the decrease in heart O2 consumption and prevented the decrease in ventricular contractile and lusitropic reserve in ROFA-exposed mice. Moreover, infliximab-pretreated ROFA-exposed mice showed conserved left ventricular developed pressure and cardiac O2 consumption in response to a β-adrenergic stimulus with isoproterenol. These results provides direct evidence linking systemic inflammation and altered cardiac function following an acute exposure to PM and contribute to the understanding of PM-associated cardiovascular morbidity and mortality.

scholarly journals The TRH Gene Is Regulated by Thyroid Hormone at the Level of Transcription in Vivo

2010 ◽  
Vol 31 (1) ◽  
pp. 136-136
Author(s):  
Michelle L. Sugrue ◽  
Kristen R. Vella ◽  
Crystal Morales ◽  
Marisol E. Lopez ◽  
Anthony N. Hollenberg
Keyword(s):  
Thyroid Hormone ◽  
Genomic Region ◽  
Model System ◽  
Model Systems ◽  
In Vivo Model ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Normal Production

ABSTRACT The expression of the TRH gene in the paraventricular nucleus (PVH) of the hypothalamus is required for the normal production of thyroid hormone (TH) in rodents and humans. In addition, the regulation of TRH mRNA expression by TH, specifically in the PVH, ensures tight control of the set point of the hypothalamic-pituitary-thyroid axis. Although many studies have assumed that the regulation of TRH expression by TH is at the level of transcription, there is little data available to demonstrate this. We used two in vivo model systems to show this. In the first model system, we developed an in situ hybridization (ISH) assay directed against TRH heteronuclear RNA to measure TRH transcription directly in vivo. We show that in the euthyroid state, TRH transcription is present both in the PVH and anterior/lateral hypothalamus. In the hypothyroid state, transcription is activated in the PVH only and can be shut off within 5 h by TH. In the second model system, we employed transgenic mice that express the Cre recombinase under the control of the genomic region containing the TRH gene. Remarkably, TH regulates Cre expression in these mice in the PVH only. Taken together, these data affirm that TH regulates TRH at the level of transcription in the PVH only and that genomic elements surrounding the TRH gene mediate its regulation by T3. Thus, it should be possible to identify the elements within the TRH locus that mediate its regulation by T3 using in vivo approaches.

scholarly journals Minireview: The Neural Regulation of the Hypothalamic-Pituitary-Thyroid Axis

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4128-4135 ◽  
Author(s):  
Ricardo H. Costa-e-Sousa ◽  
Anthony N. Hollenberg
Keyword(s):  
Thyroid Hormone ◽  
Adult Life ◽  
Feedback System ◽  
Primary Hypothyroidism ◽  
Neural Regulation ◽  
Pituitary Thyroid Axis ◽  
Genes Encoding ◽  
Thyroid Axis ◽  
Hpt 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. In humans and other vertebrates, it is well known that TH negatively regulates its own production through central actions that modulate the hypothalamic-pituitary-thyroid (HPT) axis. Indeed, primary hypothyroidism leads to the up-regulation of the genes encoding many key players in the HPT axis, such as TRH, type 2 deiodinase (dio2), pyroglutamyl peptidase II (PPII), TRH receptor 1 (TRHR1), and the TSH α- and β-subunits. However, in many physiological circumstances, the activity of the HPT axis is not always a function of circulating TH concentrations. Indeed, circadian changes in the HPT axis activity are not a consequence of oscillation in circulating TH levels. Similarly, during reduced food availability, several components of the HPT axis are down-regulated even in the presence of lower circulating TH levels, suggesting the presence of a regulatory pathway hierarchically higher than the feedback system. This minireview discusses the neural regulation of the HPT axis, focusing on both TH-dependent and -independent pathways and their potential integration.

scholarly journals The Nuclear Receptor Corepressor (NCoR) Controls Thyroid Hormone Sensitivity and the Set Point of the Hypothalamic-Pituitary-Thyroid Axis

2011 ◽  
Vol 25 (2) ◽  
pp. 212-224 ◽  
Author(s):  
Inna Astapova ◽  
Kristen R. Vella ◽  
Preeti Ramadoss ◽  
Kaila A. Holtz ◽  
Benjamin A. Rodwin ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Nuclear Receptor ◽  
Hormone Sensitivity ◽  
Set Point ◽  
Nuclear Receptor Corepressor ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis
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