en
Scientific article
Open access
English

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

Published inFolia biologica, vol. 63, no. 2, p. 60-66
Publication date2017
Abstract

Production of thyroid hormone is precisely regulated in a negative feed-back mechanism that depends critically on thyroid hormone receptor β (TRβ). 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. TRβ, 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 TRβ have been identified to date. Here, we hypothesized that additional pathogenic mutations in TRβ 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 TRβ, including a previously unknown mutation, T273R. This suggests that threonine 273 is likely to be critical for the normal function of TRβ, possibly due to its role in helix 12 mobility and interaction with coactivators, and thus supports the concept that TRβ-dependent trans-activating function is necessary for the inhibition of TRH and TSH expression in response to elevated levels of TH.

eng
Keywords
  • Female
  • Humans
  • Hypothalamus / metabolism
  • Male
  • Mutation
  • Thyroid Hormone Receptors beta / genetics
  • Thyroid Hormones / metabolism
  • Thyrotropin / metabolism
  • Thyrotropin-Releasing Hormone / metabolism
Affiliation Not a UNIGE publication
Citation (ISO format)
KASSAK, Filip et al. Novel Mutation (T273R) in Thyroid Hormone Receptor β Gene Provides Further Insight into Cryptic Negative Regulation by Thyroid Hormone. In: Folia biologica, 2017, vol. 63, n° 2, p. 60–66.
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal0015-5500
11views
4downloads

Technical informations

Creation07/19/2023 12:19:56 PM
First validation10/05/2023 6:42:31 AM
Update time10/05/2023 6:42:31 AM
Status update10/05/2023 6:42:31 AM
Last indexation02/12/2024 1:49:13 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack