9-cis-retinoic acid inhibits androgen receptor activity through activation of retinoid X receptor

Mol Endocrinol. 2005 May;19(5):1200-12. doi: 10.1210/me.2004-0181. Epub 2005 Jan 13.


Although the retinoic X receptor (RXR) forms heterodimers with many members of the estrogen receptor subfamily, the interaction between RXR and the members of the glucocorticoid receptor subfamily remains unclear. Here we show that the RXR can form a heterodimer with the androgen receptor (AR) under in vitro and in vivo conditions. Functional analyses further demonstrated that the AR, in the presence or absence of androgen, can function as a repressor to suppress RXR target genes, thereby preventing the RXR binding to the RXR DNA response element. In contrast, RXR can function as a repressor to suppress AR target genes in the presence of 9-cis-retinoic acid, but unliganded RXR can function as a weak coactivator to moderately enhance AR transactivation. Together, these results not only reveal a unique interaction between members of the two nuclear receptor subfamilies, but also represent the first evidence showing a nuclear receptor (RXR) may function as either a repressor or a coactivator based on the ligand binding status.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alitretinoin
  • Antineoplastic Agents / pharmacology*
  • Dimerization
  • Gene Expression / drug effects*
  • Glutathione Transferase
  • Promoter Regions, Genetic / physiology
  • Prostate-Specific Antigen / genetics
  • Prostate-Specific Antigen / metabolism
  • Protein Structure, Tertiary
  • Receptors, Androgen / metabolism*
  • Response Elements / physiology
  • Retinoid X Receptors / metabolism*
  • Transcriptional Activation
  • Tretinoin / pharmacology*


  • Antineoplastic Agents
  • Receptors, Androgen
  • Retinoid X Receptors
  • Alitretinoin
  • Tretinoin
  • Glutathione Transferase
  • Prostate-Specific Antigen