Ligand-dependent contribution of RXRβ to cholesterol homeostasis in Sertoli cells

Bénédicte Mascrez; Norbert B. Ghyselinck; Mitsuhiro Watanabe; Jean Sébastien Annicotte; Pierre Chambon; Johan Auwerx; Manuel Mark

doi:10.1038/sj.embor.7400094

Ligand-dependent contribution of RXRβ to cholesterol homeostasis in Sertoli cells

Bénédicte Mascrez, Norbert B. Ghyselinck, Mitsuhiro Watanabe, Jean Sébastien Annicotte, Pierre Chambon, Johan Auwerx, Manuel Mark

Research output: Contribution to journal › Article › peer-review

57 Citations (Scopus)

Abstract

We show that mice expressing retinoid X receptor β (RXRβ) impaired in its transcriptional activation function AF-2 (Rxrb^af20 mutation) do not display the spermatid release defects observed in RXRβ-null mutants, indicating that the role of RXRβ in spermatid release is ligand-independent. In contrast, like RXRβ-null mutants, Rxrb^af20 mice accumulate cholesteryl esters in Sertoli cells (SCs) due to reduced ABCA1 transporter-mediated cholesterol efflux. We provide genetic and molecular evidence that cholesterol homeostasis in SCs does not require PPARα and β, but depends upon the TIF2 coactivator and RXRβ/LXRβ heterodimers, in which RXRβ AF-2 is transcriptionally active. Our results also indicate that RXRβ may be activated by a ligand distinct from 9-cis retinoic acid.

Original language	English
Pages (from-to)	285-290
Number of pages	6
Journal	EMBO Reports
Volume	5
Issue number	3
DOIs	https://doi.org/10.1038/sj.embor.7400094
Publication status	Published - 2004 Mar
Externally published	Yes

Keywords

ABC transporters
Fatty degeneration
LXR
Retinoic acid
Spermatogenesis

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics

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10.1038/sj.embor.7400094

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title = "Ligand-dependent contribution of RXRβ to cholesterol homeostasis in Sertoli cells",

abstract = "We show that mice expressing retinoid X receptor β (RXRβ) impaired in its transcriptional activation function AF-2 (Rxrbaf20 mutation) do not display the spermatid release defects observed in RXRβ-null mutants, indicating that the role of RXRβ in spermatid release is ligand-independent. In contrast, like RXRβ-null mutants, Rxrbaf20 mice accumulate cholesteryl esters in Sertoli cells (SCs) due to reduced ABCA1 transporter-mediated cholesterol efflux. We provide genetic and molecular evidence that cholesterol homeostasis in SCs does not require PPARα and β, but depends upon the TIF2 coactivator and RXRβ/LXRβ heterodimers, in which RXRβ AF-2 is transcriptionally active. Our results also indicate that RXRβ may be activated by a ligand distinct from 9-cis retinoic acid.",

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author = "B{\'e}n{\'e}dicte Mascrez and Ghyselinck, {Norbert B.} and Mitsuhiro Watanabe and Annicotte, {Jean S{\'e}bastien} and Pierre Chambon and Johan Auwerx and Manuel Mark",

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AU - Mascrez, Bénédicte

AU - Ghyselinck, Norbert B.

AU - Watanabe, Mitsuhiro

AU - Annicotte, Jean Sébastien

AU - Chambon, Pierre

AU - Auwerx, Johan

AU - Mark, Manuel

PY - 2004/3

Y1 - 2004/3

N2 - We show that mice expressing retinoid X receptor β (RXRβ) impaired in its transcriptional activation function AF-2 (Rxrbaf20 mutation) do not display the spermatid release defects observed in RXRβ-null mutants, indicating that the role of RXRβ in spermatid release is ligand-independent. In contrast, like RXRβ-null mutants, Rxrbaf20 mice accumulate cholesteryl esters in Sertoli cells (SCs) due to reduced ABCA1 transporter-mediated cholesterol efflux. We provide genetic and molecular evidence that cholesterol homeostasis in SCs does not require PPARα and β, but depends upon the TIF2 coactivator and RXRβ/LXRβ heterodimers, in which RXRβ AF-2 is transcriptionally active. Our results also indicate that RXRβ may be activated by a ligand distinct from 9-cis retinoic acid.

AB - We show that mice expressing retinoid X receptor β (RXRβ) impaired in its transcriptional activation function AF-2 (Rxrbaf20 mutation) do not display the spermatid release defects observed in RXRβ-null mutants, indicating that the role of RXRβ in spermatid release is ligand-independent. In contrast, like RXRβ-null mutants, Rxrbaf20 mice accumulate cholesteryl esters in Sertoli cells (SCs) due to reduced ABCA1 transporter-mediated cholesterol efflux. We provide genetic and molecular evidence that cholesterol homeostasis in SCs does not require PPARα and β, but depends upon the TIF2 coactivator and RXRβ/LXRβ heterodimers, in which RXRβ AF-2 is transcriptionally active. Our results also indicate that RXRβ may be activated by a ligand distinct from 9-cis retinoic acid.

KW - ABC transporters

KW - Fatty degeneration

KW - LXR

KW - Retinoic acid

KW - Spermatogenesis

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IS - 3

ER -

Ligand-dependent contribution of RXRβ to cholesterol homeostasis in Sertoli cells

Abstract

Keywords

ASJC Scopus subject areas

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