Gene expression of T3-regulated genes in a mouse model of the human thyroid hormone resistance

Thyroid hormone resistance - we might have a bit more of a clue...

Life Sci. 2016 Dec 2. pii: S0024-3205(16)30682-8. doi: 10.1016/j.lfs.2016.11.032. [Epub ahead of print]

Gene expression of T3-regulated genes in a mouse model of the human thyroid hormone resistance.

Santiago LA1, Faustino LC1, Pereira GF1, Imperio GE1, Pazos-Moura CC2, Wondisford FE3, Bloise FF1, Ortiga-Carvalho TM4.

Author information

1Laboratório de Endocrinologia Translacional, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

2Laboratório de Endocrinologia Molecular, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.

3Department of Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

4Laboratório de Endocrinologia Translacional, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. Electronic address: taniaort@biof.ufrj.br.

Abstract

AIMS:

To understand how thyroid hormone (TH) regulates tissue-specific gene expression in patients with the syndrome of resistance to TH (RTHβ), we used a mouse model that replicates the human RTHβ, specifically the ∆337T mutation in the thyroid hormone receptor β (THRβ).

MAIN METHODS:

We investigated the expression of key TH target genes in the pituitary and liver of TRβ∆337T and wild type THRβ mice by qPCR before and after a T3 suppression test consisting of the administration of increasing concentrations of T3 to hypothyroid mice.

KEY FINDINGS:

PituitaryTshb and Cga expression decreased and Gh expression increased in TRβ∆337T mice after T3 suppression. The stimulation of positively regulated TH genes was heterogeneous in the liver. Levels of liver Me1 and Thsrp were elevated in TRβ∆337T mice after T3 administration. Slc16a2 and Gpd2 did not respond to T3 stimulation in the liver of TRβ∆337T mice whereas Dio1 response was lower than that observed in WT mice. Moreover, although Chdh and Upd1 genes were negatively regulated in the liver, the expression of these genes was elevated after T3 suppression. We did not observe significant changes in THRα expression in the liver and pituitary, while THRβ levels were diminished in the pituitary and increased in the liver.

SIGNIFICANCE:

Using a model expressing a THRβ unable to bind T3, we showed the expression pattern of liver negative and positive regulated genes by T3.

Copyright © 2016. Published by Elsevier Inc.

KEYWORDS:

Gene expression; Liver; Thyroid hormone receptor

PMID: 27919825

DOI: 10.1016/j.lfs.2016.11.032

[PubMed - as supplied by publisher]

ncbi.nlm.nih.gov/pubmed/279...

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