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

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.