Auto-Regulation of the Thyroid Gland Beyond Classical Pathways

2020 ◽  
Vol 128 (06/07) ◽  
pp. 437-445 ◽  
Author(s):  
Klaudia Brix ◽  
Joanna Szumska ◽  
Jonas Weber ◽  
Maria Qatato ◽  
Vaishnavi Venugopalan ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Hormone Receptors ◽  
Self Regulation ◽  
Thyroid Stimulating Hormone ◽  
Apical Plasma Membrane ◽  
Deficient Mice ◽  
Stimulating Hormone

AbstractThis mini-review asks how self-regulation of the thyroid gland is realized at the cellular and molecular levels by canonical and non-canonical means. Canonical pathways of thyroid regulation comprise thyroid stimulating hormone-triggered receptor signaling. As part of non-canonical regulation, we hypothesized an interplay between protease-mediated thyroglobulin processing and thyroid hormone release into the circulation by means of thyroid hormone transporters like Mct8. We proposed a sensing mechanism by different thyroid hormone transporters, present in specific subcellular locations of thyroid epithelial cells, selectively monitoring individual steps of thyroglobulin processing, and thus, the cellular thyroid hormone status. Indeed, we found that proteases and thyroid hormone transporters are functionally inter-connected, however, in a counter-intuitive manner fostering self-thyrotoxicity in particular in Mct8- and/or Mct10-deficient mice. Furthermore, the possible role of the G protein-coupled receptor Taar1 is discussed, because we detected Taar1 at cilia of the apical plasma membrane of thyrocytes in vitro and in situ. Eventually, through pheno-typing Taar1-deficient mice, we identified a co-regulatory role of Taar1 and the thyroid stimulating hormone receptors. Recently, we showed that inhibition of thyroglobulin-processing enzymes results in disappearance of cilia from the apical pole of thyrocytes, while Taar1 is re-located to the endoplasmic reticulum. This pathway features a connection between thyrotropin-stimulated secretion of proteases into the thyroid follicle lumen and substrate-mediated self-assisted control of initially peri-cellular thyroglobulin processing, before its reinternalization by endocytosis, followed by extensive endo-lysosomal liberation of thyroid hormones, which are then released from thyroid follicles by means of thyroid hormone transporters.

scholarly journals Congenital Hypothyroidism (Cretinism) in neuroD2-Deficient Mice

2006 ◽  
Vol 26 (11) ◽  
pp. 4311-4315 ◽  
Author(s):  
Chin-Hsing Lin ◽  
Stephen J. Tapscott ◽  
James M. Olson
Keyword(s):  
Transcription Factor ◽  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Anterior Lobe ◽  
Thyroid Stimulating Hormone ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
Hypothalamic Nuclei ◽  
Hpt Axis ◽  
Deficient Mice

ABSTRACT Mice lacking neuroD2, a basic helix-loop-helix transcription factor involved in brain development, show growth retardation and other abnormalities consistent with hypothalamic-pituitary-thyroid (HPT) axis dysfunction. neuroD2 is expressed in the paraventricular hypothalamic nuclei, the anterior lobe of pituitary, and the thyroid gland. In neuroD2-deficient mice, thyrotropin-releasing hormone, thyroid-stimulating hormone, and thyroid hormone are decreased in these three regions, respectively. neuroD2-null mice typically die 2 to 3 weeks after birth, but those treated with replacement doses of thyroxine survived more than 8 weeks. These data indicate that neuroD2 is expressed throughout the HPT axis and that all levels of the axis are functionally affected by its absence in mice.

scholarly journals The Ability of Thyroid Hormone Receptors to Sense T4 as an Agonist Depends on Receptor Isoform and on Cellular Cofactors

2014 ◽  
Vol 28 (5) ◽  
pp. 745-757 ◽  
Author(s):  
Amy Schroeder ◽  
Robyn Jimenez ◽  
Briana Young ◽  
Martin L. Privalsky
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptor ◽  
Cell Types ◽  
Receptor Associated Protein ◽  
Steroid Receptor Coactivator ◽  
Different Cell Types

Abstract T4 (3,5,3′,5′-tetraiodo-l-thyronine) is classically viewed as a prohormone that must be converted to the T3 (3,5,3′-triiodo-l-thyronine) form for biological activity. We first determined that the ability of reporter genes to respond to T4 and to T3 differed for the different thyroid hormone receptor (TR) isoforms, with TRα1 generally more responsive to T4 than was TRβ1. The response to T4 vs T3 also differed dramatically in different cell types in a manner that could not be attributed to differences in deiodinase activity or in hormone affinity, leading us to examine the role of TR coregulators in this phenomenon. Unexpectedly, several coactivators, such as steroid receptor coactivator-1 (SRC1) and thyroid hormone receptor-associated protein 220 (TRAP220), were recruited to TRα1 nearly equally by T4 as by T3 in vitro, indicating that TRα1 possesses an innate potential to respond efficiently to T4 as an agonist. In contrast, release of corepressors, such as the nuclear receptor coreceptor NCoRω, from TRα1 by T4 was relatively inefficient, requiring considerably higher concentrations of this ligand than did coactivator recruitment. Our results suggest that cells, by altering the repertoire and abundance of corepressors and coactivators expressed, may regulate their ability to respond to T4, raising the possibility that T4 may function directly as a hormone in specific cellular or physiological contexts.

Thyroid-stimulating hormone receptor and thyroid hormone receptors are involved in human endometrial physiology

2011 ◽  
Vol 95 (1) ◽  
pp. 230-237.e2 ◽  
Author(s):  
Lusine Aghajanova ◽  
Anneli Stavreus-Evers ◽  
Maria Lindeberg ◽  
Britt-Marie Landgren ◽  
Lottie Skjöldebrand Sparre ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Hormone Receptors ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Hormone Receptors ◽  
Stimulating Hormone

Effect of thyroid hormone on myocardial catecholamine content of the guinea pig

1961 ◽  
Vol 201 (6) ◽  
pp. 1049-1052 ◽  
Author(s):  
M. Jay Goodkind ◽  
David H. Fram ◽  
Michael Roberts
Keyword(s):  
Thyroid Hormone ◽  
Guinea Pig ◽  
Thyroid Function ◽  
Serum Protein ◽  
Guinea Pigs ◽  
Thyroid Stimulating Hormone ◽  
Catecholamine Content ◽  
Norepinephrine Content ◽  
Stimulating Hormone

Normal and thyroidectomized guinea pigs were subjected to treatment with either triiodothyronine or thyroid-stimulating hormone. Determinations of myocardial catecholamine content and serum protein-bound iodine revealed a significant increase in myocardial norepinephrine content in the markedly thyrotoxic animal, and a significant decrease in norepinephrine content of the myocardium of hypothyroid animals. The significance of these findings in defining the role of catecholamines in various states of thyroid function is discussed.

scholarly journals Protective role of ascorbic acid on lead-induced damage to the thyroid gland in the rat

2020 ◽  
Vol 9 (5) ◽  
pp. 632-635
Author(s):  
Denisse Calderón-Vallejo ◽  
María del Carmen Díaz-Galindo ◽  
Andrés Quintanar-Stephano ◽  
Carlos Olvera-Sandoval ◽  
J Luis Quintanar
Keyword(s):  
Ascorbic Acid ◽  
Drinking Water ◽  
Thyroid Gland ◽  
Lead Poisoning ◽  
Lead Acetate ◽  
Protective Action ◽  
Protective Role ◽  
Thyroid Stimulating Hormone ◽  
Stimulating Hormone

Abstract Lead exposure is known to affect the pituitary-thyroid axis. Likewise, ascorbic acid (AA) has a protective action against lead poisoning. We examine the protective role of AA in lead-induced damage to the thyroid gland. The Wistar rats were divided into three groups: control that received 0.2% AA in drinking water throughout the experiment (15 days), intoxicated with lead acetate (20 mg/kg) intraperitoneally every 48 h for 15 days, and the experimental group treated with lead acetate and 0.2% AA in drinking water throughout the experiment. Plasma thyroid-stimulating hormone, triiodothyronine, thyroxine, and lead were determined. The thyroid gland was weighed, then epithelial cell height and nuclear volume were measured on histological slides. The results show that AA reduced the thyroid atrophy caused by lead acetate, as well as the loss of weight of the gland. In addition, it prevented the decrease of the hormone triiodothyronine, although the thyroxine hormone remained lower than the control values ​​and the thyroid-stimulating hormone remains high. Our results indicated that AA could play a protective role in lead poisoning in the thyroid gland.

H9c2 cardiomyoblasts produce thyroid hormone

2008 ◽  
Vol 294 (5) ◽  
pp. C1227-C1233 ◽  
Author(s):  
Christof Meischl ◽  
Henk P. Buermans ◽  
Thierry Hazes ◽  
Marian J. Zuidwijk ◽  
René J. P. Musters ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Peroxidase ◽  
Sodium Iodide Symporter ◽  
Hormone Synthesis ◽  
Cardiovascular Hemodynamics ◽  
Wide Range ◽  
Vitro Model

Thyroid hormone acts on a wide range of tissues. In the cardiovascular system, thyroid hormone is an important regulator of cardiac function and cardiovascular hemodynamics. Although some early reports in the literature suggested an unknown extrathyroidal source of thyroid hormone, it is currently thought to be produced exclusively in the thyroid gland, a highly specialized organ with the sole function of generating, storing, and secreting thyroid hormone. Whereas most of the proteins necessary for thyroid hormone synthesis are thought to be expressed exclusively in the thyroid gland, we now have found evidence that all of these proteins, i.e., thyroglobulin, DUOX1, DUOX2, the sodium-iodide symporter, pendrin, thyroid peroxidase, and thyroid-stimulating hormone receptor, are also expressed in cardiomyocytes. Furthermore, we found thyroglobulin to be transiently upregulated in an in vitro model of ischemia. When performing these experiments in the presence of 125I, we found that 125I was integrated into thyroglobulin and that under ischemia-like conditions the radioactive signal in thyroglobulin was reduced. Concomitantly we observed an increase of intracellularly produced, 125I-labeled thyroid hormone. In conclusion, our findings demonstrate for the first time that cardiomyocytes produce thyroid hormone in a manner adapted to the cell's environment.

THE INHIBITION OF [35S]THIOCYANATE METABOLISM IN THE THYROID GLAND BY THYROID-STIMULATING HORMONE

1972 ◽  
Vol 52 (2) ◽  
pp. 219-227 ◽  
Author(s):  
S. BOBEK
Keyword(s):  
Thyroid Gland ◽  
Chromatographic Analysis ◽  
Thyroid Stimulating Hormone ◽  
Unit Weight ◽  
Control Group ◽  
Percentage Content ◽  
Influence Of Tsh ◽  
Stimulating Hormone

SUMMARY When potassium [35S]thiocyanate was administered to rats, treatment with thyroid-stimulating hormone (TSH) diminished the amount of 35S per unit weight of thyroid, as well as the thyroid:plasma 35S ratio (T:P) for compounds containing 35S. Chromatographic analysis of thyroid gland homogenates and plasma showed that under the influence of TSH the 35SCN-fraction increased, while the 35SO42− fraction decreased in the thyroid. The T:P ratio calculated for both fractions confirmed the increase of the 35SCN-concentration in the thyroid. Chromatographic analysis of the plasma showed that the 35SCN− fraction in the TSH-treated animals increased gradually while it decreased in the control group. Experiments with guinea-pig thyroid lobes in vitro agreed with the results in vivo. A significant increase of 35SCN− and a decrease in 35SO42− were found in TSH-treated thyroids after 6 h of incubation. Even clearer results were obtained by analysis of the medium. Oxidation of [35S]thiocyanate to [35S]sulphate, with a simultaneous release into the medium of the latter, took place only in the control thyroid lobes. In the TSH-treated thyroids, no changes were found in the percentage content of 35S compounds in the medium during 6 h of incubation. These results suggest that TSH inhibits the degradation of thiocyanate in the thyroid.

Sign in / Sign up

Export Citation Format

Share Document