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

被引：58

作者：

Mascrez, B ^{[1
]}

Ghyselinck, NB ^{[1
]}

Watanabe, M ^{[1
]}

Annicotte, JS ^{[1
]}

Chambon, P ^{[1
]}

Auwerx, J ^{[1
]}

Mark, M ^{[1
]}

机构：

[1] Coll France, ULP, INSERM,CNRS,Inst Clin Souris, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, CU De Strasbour, France

来源：

EMBO REPORTS | 2004年 / 5卷 / 03期

关键词：

ABC transporters; fatty degeneration; LXR; retinoic acid; spermatogenesis;

D O I：

10.1038/sj.embor.7400094

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We show that mice expressing retinoid X receptor beta (RXRbeta) impaired in its transcriptional activation function AF-2 (Rxrb(af20) mutation) do not display the spermatid release defects observed in RXRbeta-null mutants, indicating that the role of RXRbeta in spermatid release is ligand-independent. In contrast, like RXRbeta-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 PPARalpha and beta, but depends upon the TIF2 coactivator and RXRbeta/LXRbeta heterodimers, in which RXRbeta AF-2 is transcriptionally active. Our results also indicate that RXRbeta may be activated by a ligand distinct from 9-cis retinoic acid.

引用

收藏

页码：285 / 290

页数：6

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