Novel Mutation (T273R) in Thyroid Hormone Receptor beta Gene Provides Further Insight into Cryptic Negative Regulation by Thyroid Hormone

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10363989" target="_blank" >RIV/00216208:11110/17:10363989 - isvavai.cz</a>

Result on the web

<a href="http://fb.cuni.cz/file/5839/fb2017a0010.pdf" target="_blank" >http://fb.cuni.cz/file/5839/fb2017a0010.pdf</a>

DOI - Digital Object Identifier

—

Result language

angličtina

Original language name

Novel Mutation (T273R) in Thyroid Hormone Receptor beta Gene Provides Further Insight into Cryptic Negative Regulation by Thyroid Hormone

Original language description

Production of thyroid hormone is precisely regulated in a negative feed-back mechanism that depends critically on thyroid hormone receptor beta (TR beta). This mechanism decreases production of thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) in the hypothalamus and pituitary gland in response to high levels of circulating thyroid hormones (TH). Despite the wealth of accumulated knowledge, it is still not clear how exactly this negative regulation is executed. The syndrome of resistance to thyroid hormone (RTH), in which the levels of TH are not properly sensed, represents naturally occurring situations in which molecular components of this regulation are displayed and may be uncovered. TR beta, which is central to this regulation, is in the majority of RTH cases mutated in a way that preserves some functions of the receptor. Approximately 150 different mutations in TR beta have been identified to date. Here, we hypothesized that additional pathogenic mutations in TR beta are likely to exist in human population and analysed clinical cases with suspected RTH. In keeping with our prediction, analysis of 17 patients from nine families led to identification of four presumed pathogenic mutations of TR beta, including a previously unknown mutation, T273R. This suggests that threonine 273 is likely to be critical for the normal function of TR beta, possibly due to its role in helix 12 mobility and interaction with coactivators, and thus supports the concept that TR beta-dependent trans-activating function is necessary for the inhibition of TRH and TSH expression in response to elevated levels of TH.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30202 - Endocrinology and metabolism (including diabetes, hormones)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Folia Biologica

ISSN

0015-5500

e-ISSN

—

Volume of the periodical

63

Issue of the periodical within the volume

2

Country of publishing house

CZ - CZECH REPUBLIC

Number of pages

7

Pages from-to

60-66

UT code for WoS article

000403328800004

EID of the result in the Scopus database

2-s2.0-85019999245