Thyroid Hormones
Hormones acting through Nuclear Receptors

Author: Gianpiero Pescarmona
Date: 22/03/2007

Description

The Thyroid hormones

The Gland

more anatomy
Thyroid vessels

The thyroid gland is
located around the trachea
and its blood flow is
sensitive to the
respiratory rate

The Hormone

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The Synthesis

Requirements:

Iodine uptake into the thyrocytes

Active transport of iodide into the thyroid gland is a crucial and rate-limiting step in the biosynthesis of thyroid hormones. It is mediated by a specific sodium-dependent iodide transporter located at the basolateral membrane of thyroid follicular cells, the sodium iodide symporter - NIS, C Spitzweg, JC. Morris, 2002.

The Release

Role of thyroglobulin endocytic pathways in the control of thyroid hormone release 2000

The degradation

Iodotyrosine deiodinase (a member of the NADH oxidase/flavin reductase family) activity is regulated by NADH/NAD ratio

a deeper insight

Drugs effecting TH function

Iodine uptake into the thyrocytes

Active transport of iodide into the thyroid gland is a crucial and rate-limiting step in the biosynthesis of thyroid hormones. It is mediated by a specific sodium-dependent iodide transporter located at the basolateral membrane of thyroid follicular cells, the sodium iodide symporter - NIS.

Pituitary-derived TSH had been known for decades to stimulate iodide transport into the thyroid gland via the adenylate cyclase cAMP pathway

The iodine metabolism according to L. Fugazzola -

Redox up-regulated expression of rat liver manganese superoxide dismutase and Bcl-2 by thyroid hormone is associated with inhibitor of κB-α phosphorylation and nuclear factor-κB activation
Fernandez V;
JOURNAL OF ENDOCRINOLOGY
2005, Volume: 186(3) Page(s): 539-547

The Circadian Rythm

TH Target Tissues

TH enter and are metabolized differently in different tissues

TH resistance

Papers TSH NCoR

The Nuclear Receptor Corepressor (NCoR) Controls Thyroid Hormone Sensitivity and the Set Point of the Hypothalamic-Pituitary-Thyroid Axis. 2008

The role of nuclear receptor corepressor (NCoR) in thyroid hormone (TH) action has been difficult to discern because global deletion of NCoR is embryonic lethal. To circumvent this, we developed mice that globally express a modified NCoR protein (NCoRΔID) that cannot be recruited to the thyroid hormone receptor (TR). These mice present with low serum T(4) and T(3) concentrations accompanied by normal TSH levels, suggesting central hypothyroidism. However, they grow normally and have increased energy expenditure and normal or elevated TR-target gene expression across multiple tissues, which is not consistent with hypothyroidism. Although these findings imply an increased peripheral sensitivity to TH, the hypothalamic-pituitary-thyroid axis is not more sensitive to acute changes in TH concentrations but appears to be reset to recognize the reduced TH levels as normal. Furthermore, the thyroid gland itself, although normal in size, has reduced levels of nonthyroglobulin-bound T(4) and T(3) and demonstrates decreased responsiveness to TSH. Thus, the TR-NCoR interaction controls systemic TH sensitivity as well as the set point at all levels of the hypothalamic-pituitary-thyroid axis. These findings suggest that NCoR levels could alter cell-specific TH action that would not be reflected by th

Hypothyroidism

Comments
2012-12-26T11:20:33 - Gianpiero Pescarmona

Mittag Jens J Clin Invest. Heart brain thyroid

omeprazole thyroid

2010-01-29T01:52:09 - Paolo Fornaciari

p=

Paolo Fornaciari, Giulia Cossu

2008-07-02T10:00:08 - Gianpiero Pescarmona

Think globally: Act locally: New insights into the local regulation of thyroid hormone availability challenge long accepted dogmas, 2008

Amphibian metamorphosis as a model for the developmental actions of thyroid hormone, 2006

The regolation of thyroid function: T3 and T4 production
Thyroxine is synthesised by the follicular cells from free tyrosine and on the tyrosine residues of the protein called thyroglobulin (TG).
Inorganic iodine enters the body primarily as iodide, I-. After entering the thyroid follicle (or thyroid follicular cell) via a Na+/I- symporter (NIS) on the basolateral side, iodide is shuttled across the apical membrane into the colloid via pendrin, after which thyroid peroxidase oxidizes iodide to atomic iodine (I) or iodinium (I+). The "organification of iodine," the incorporation of iodine to thyroglobulin for the production of thyroid hormone is inseparable from oxidation and is catalyzed by TPO. The chemical reactions catalyzed by thyroid peroxidase occur on the outer apical membrane surface and are mediated by hydrogen peroxide. Upon stimulation by the thyroid-stimulating hormone (TSH), the follicular cells reabsorb TG and proteolytically cleave the iodinated tyrosines from TG, forming T4 and T3, and releasing them into the blood. Thyroid hormone that is secreted from the gland is about 90% T4 and about 10% T3.

Deiodinase is an enzyme important in the action of thyroid hormones; it is a selenium-dipendent enzyme. Deiodinases are unusual in that the enzyme contains selenium, in the form of an otherwise rare amino acid selenocysteine.
In the tissues, deiodinases can either activate or inactivate thyroid hormones:
• Activation occurs by conversion of the prohormone thyroxine (T4) to the active hormone triiodothyronine (T3) through the removal of an iodine atom on the outer ring.
• Inactivation of thyroid hormones occurs by removal of an iodine atom on the inner ring, which converts thyroxine to the inactive reverse triiodothyronine (rT3), or which converts the active triiodothyronine to the inactive diiodothyronine (T2). The major part of thyroxine deiodination occurs within the cells.

2007-05-29T20:14:35 - Alberto Iuso

Thyroid hormones role

Physiological and Molecular Basis

of Thyroid Hormone Action 2001

2007-05-29T16:04:19 - Francesco Andrea Coero Borga

Impact of placental hormone withdrawal on postpartum depression

In uno studio condotto su 20 donne che presentano una depressione post parto e altre 20 senza depressione post parto, sono stati misurati il livelli di progesterone, estradiolo e l'ormone gonadotropina corionica.

Il risultato è interessante perchè l'effetto depressivo è scatenato da una più veloce perdita dell'ormone gonadotropina corionica nelle donne affette da depressione rispetto a quelle senza depressione post parto.

L'effetto depressivo potrebbe essere quindi correlato alla mancanza di TSH dovuto ad una troppo veloce perdita dell'ormone gonadotropina corionica (che durante la gravidanza vicaria l'azione del TSH facendo produrre tanto ormone tiroideo).
Se manca l'ormone tiroideo mancherà alle cellule ATP....SNC meno vivace!

2007-03-30T20:31:05 - Gianpiero Pescarmona

Medpilot thyroid+hormone+receptor+aging

Expression of thyroid hormone receptors A and B in developing rat tissues; evidence for extensive posttranscriptional regulation. 2007

TH and lipoproteins

Beneficial effects of a novel thyromimetic on lipoprotein metabolism. 1997

THYROMIMETIC LIPOPROTEIN

Thyroid hormones and thyroid hormone receptors: effects of thyromimetics on reverse cholesterol transport.2010 Fulltext
World J Gastroenterol. 2010 Dec 21;16(47):5958-64.
Pedrelli M, Pramfalk C, Parini P.

Reverse cholesterol transport (RCT) is a complex process which transfers cholesterol from peripheral cells to the liver for subsequent elimination from the body via feces. Thyroid hormones (THs) affect growth, development, and metabolism in almost all tissues. THs exert their actions by binding to thyroid hormone receptors (TRs). There are two major subtypes of TRs, TRα and TRβ, and several isoforms (e.g. TRα1, TRα2, TRβ1, and TRβ2). Activation of TRα1 affects heart rate, whereas activation of TRβ1 has positive effects on lipid and lipoprotein metabolism. Consequently, particular interest has been focused on the development of thyromimetic compounds targeting TRβ1, not only because of their ability to lower plasma cholesterol but also due their ability to stimulate RCT, at least in pre-clinical models. In this review we focus on THs, TRs, and on the effects of TRβ1-modulating thyromimetics on RCT in various animal models and in humans.

non sono d'accordo
voce bibliografica

On commonness and rarity of thyroid hormone resistance: A discussion based on mechanisms of reduced sensitivity 2007


Decrease in mitochondrial energy coupling by thyroid hormones: a physiological effect rather than a pathological hyperthyroidism consequence. 1998 Fulltext

Under the same conditions, 6-ketocholestanol appeared to be effective in recoupling of respiration uncoupled by low concentrations of the artificial protonophore FCCP.

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