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 journalArticle

56 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)285-290
Number of pages6
JournalEMBO Reports
Volume5
Issue number3
DOIs
Publication statusPublished - 2004 Mar 1
Externally publishedYes

Keywords

  • ABC transporters
  • Fatty degeneration
  • LXR
  • Retinoic acid
  • Spermatogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Mascrez, B., Ghyselinck, N. B., Watanabe, M., Annicotte, J. S., Chambon, P., Auwerx, J., & Mark, M. (2004). Ligand-dependent contribution of RXRβ to cholesterol homeostasis in Sertoli cells. EMBO Reports, 5(3), 285-290. https://doi.org/10.1038/sj.embor.7400094