Thyroid hormones, T3 and T4, in the brain

Amy C. Schroeder, Martin L. Privalsky

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Thyroid hormones (THs) are essential for fetal and post-natal nervous system development and also play an important role in the maintenance of adult brain function. Of the two major THs, T4 (3,5,3',5'-tetraiodo-l-thyronine) is classically viewed as an pro-hormone that must be converted to T3 (3,5,3'-tri-iodo-l-thyronine) via tissue-level deiodinases for biological activity. THs primarily mediate their effects by binding to thyroid hormone receptor (TR) isoforms, predominantly TRa1 and TRβ1, which are expressed in different tissues and exhibit distinctive roles in endocrinology. Notably, the ability to respond to T4 and to T3 differs for the two TR isoforms, with TRα1 generally more responsive to T4 than TRβ1. TRαis also the most abundantly expressed TR isoform in the brain, encompassing 70-80% of all TR expression in this tissue. Conversion of T4 into T3 via deiodinase 2 in astrocytes has been classically viewed as critical for generating local T3 for neurons. However, deiodinase-deficient mice do not exhibit obvious defectives in brain development or function. Considering that TRα1 is well-established as the predominant isoform in brain, and that TRa1 responds to both T3 and T4, we suggest T4 may play a more active role in brain physiology than has been previously accepted.

Original languageEnglish (US)
Article numberArticle 40
JournalFrontiers in Endocrinology
Volume5
Issue numberMAR
DOIs
StatePublished - 2014

Fingerprint

Triiodothyronine
Thyroid Hormone Receptors
Thyroxine
Iodide Peroxidase
Protein Isoforms
Thyronines
Brain
Thyroid Hormones
Endocrinology
Astrocytes
Nervous System
Maintenance
Hormones
Neurons

Keywords

  • Brain
  • Coregulator
  • Deiodinase 2
  • Thyroid hormone receptor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Thyroid hormones, T3 and T4, in the brain. / Schroeder, Amy C.; Privalsky, Martin L.

In: Frontiers in Endocrinology, Vol. 5, No. MAR, Article 40, 2014.

Research output: Contribution to journalArticle

Schroeder, Amy C. ; Privalsky, Martin L. / Thyroid hormones, T3 and T4, in the brain. In: Frontiers in Endocrinology. 2014 ; Vol. 5, No. MAR.
@article{ca1d92c3f19844769e6e44713f60687b,
title = "Thyroid hormones, T3 and T4, in the brain",
abstract = "Thyroid hormones (THs) are essential for fetal and post-natal nervous system development and also play an important role in the maintenance of adult brain function. Of the two major THs, T4 (3,5,3',5'-tetraiodo-l-thyronine) is classically viewed as an pro-hormone that must be converted to T3 (3,5,3'-tri-iodo-l-thyronine) via tissue-level deiodinases for biological activity. THs primarily mediate their effects by binding to thyroid hormone receptor (TR) isoforms, predominantly TRa1 and TRβ1, which are expressed in different tissues and exhibit distinctive roles in endocrinology. Notably, the ability to respond to T4 and to T3 differs for the two TR isoforms, with TRα1 generally more responsive to T4 than TRβ1. TRαis also the most abundantly expressed TR isoform in the brain, encompassing 70-80{\%} of all TR expression in this tissue. Conversion of T4 into T3 via deiodinase 2 in astrocytes has been classically viewed as critical for generating local T3 for neurons. However, deiodinase-deficient mice do not exhibit obvious defectives in brain development or function. Considering that TRα1 is well-established as the predominant isoform in brain, and that TRa1 responds to both T3 and T4, we suggest T4 may play a more active role in brain physiology than has been previously accepted.",
keywords = "Brain, Coregulator, Deiodinase 2, Thyroid hormone receptor",
author = "Schroeder, {Amy C.} and Privalsky, {Martin L.}",
year = "2014",
doi = "10.3389/fendo.2014.00040",
language = "English (US)",
volume = "5",
journal = "Frontiers in Endocrinology",
issn = "1664-2392",
publisher = "Frontiers Media S. A.",
number = "MAR",

}

TY - JOUR

T1 - Thyroid hormones, T3 and T4, in the brain

AU - Schroeder, Amy C.

AU - Privalsky, Martin L.

PY - 2014

Y1 - 2014

N2 - Thyroid hormones (THs) are essential for fetal and post-natal nervous system development and also play an important role in the maintenance of adult brain function. Of the two major THs, T4 (3,5,3',5'-tetraiodo-l-thyronine) is classically viewed as an pro-hormone that must be converted to T3 (3,5,3'-tri-iodo-l-thyronine) via tissue-level deiodinases for biological activity. THs primarily mediate their effects by binding to thyroid hormone receptor (TR) isoforms, predominantly TRa1 and TRβ1, which are expressed in different tissues and exhibit distinctive roles in endocrinology. Notably, the ability to respond to T4 and to T3 differs for the two TR isoforms, with TRα1 generally more responsive to T4 than TRβ1. TRαis also the most abundantly expressed TR isoform in the brain, encompassing 70-80% of all TR expression in this tissue. Conversion of T4 into T3 via deiodinase 2 in astrocytes has been classically viewed as critical for generating local T3 for neurons. However, deiodinase-deficient mice do not exhibit obvious defectives in brain development or function. Considering that TRα1 is well-established as the predominant isoform in brain, and that TRa1 responds to both T3 and T4, we suggest T4 may play a more active role in brain physiology than has been previously accepted.

AB - Thyroid hormones (THs) are essential for fetal and post-natal nervous system development and also play an important role in the maintenance of adult brain function. Of the two major THs, T4 (3,5,3',5'-tetraiodo-l-thyronine) is classically viewed as an pro-hormone that must be converted to T3 (3,5,3'-tri-iodo-l-thyronine) via tissue-level deiodinases for biological activity. THs primarily mediate their effects by binding to thyroid hormone receptor (TR) isoforms, predominantly TRa1 and TRβ1, which are expressed in different tissues and exhibit distinctive roles in endocrinology. Notably, the ability to respond to T4 and to T3 differs for the two TR isoforms, with TRα1 generally more responsive to T4 than TRβ1. TRαis also the most abundantly expressed TR isoform in the brain, encompassing 70-80% of all TR expression in this tissue. Conversion of T4 into T3 via deiodinase 2 in astrocytes has been classically viewed as critical for generating local T3 for neurons. However, deiodinase-deficient mice do not exhibit obvious defectives in brain development or function. Considering that TRα1 is well-established as the predominant isoform in brain, and that TRa1 responds to both T3 and T4, we suggest T4 may play a more active role in brain physiology than has been previously accepted.

KW - Brain

KW - Coregulator

KW - Deiodinase 2

KW - Thyroid hormone receptor

UR - http://www.scopus.com/inward/record.url?scp=84901036696&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901036696&partnerID=8YFLogxK

U2 - 10.3389/fendo.2014.00040

DO - 10.3389/fendo.2014.00040

M3 - Article

AN - SCOPUS:84901036696

VL - 5

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

SN - 1664-2392

IS - MAR

M1 - Article 40

ER -