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Androgen-receptor coregulators mediate the suppressive effect of androgen signals on vitamin D receptor activity

Huei-Ju Ting1, Bo-Ying Bao, Cheng-Lung Hsu

  • 1Department of Urology, University of Rochester, 601 Elmwood Ave., Rochester, NY 14642, USA.

Endocrine
|April 5, 2005
PubMed

Insights

Androgen receptor (AR) signaling suppresses Vitamin D Receptor (VDR) activity, potentially through competition for coactivators like ARA70. This interaction highlights a novel mechanism in VDR regulation by androgens.

Area of Science:

  • Molecular Endocrinology
  • Cellular Biology
  • Cancer Research

Background:

  • Androgen receptors (AR) and Vitamin D Receptors (VDR) are crucial nuclear receptors involved in various cellular processes.
  • AR signaling is known to influence VDR activity, but the underlying mechanisms remain incompletely understood.

Purpose of the Study:

  • To investigate the molecular mechanisms by which AR signaling suppresses VDR transactivation.
  • To identify specific AR coregulators involved in the interaction between AR and VDR.

Main Methods:

  • Utilized PC-3 and LNCaP cell lines to study AR and VDR interactions.
  • Investigated the effect of AR overexpression and 5alpha-dihydrotestosterone treatment on VDR transactivation.
  • Performed co-immunoprecipitation and transactivation assays to characterize coregulator involvement.

Main Results:

  • AR signaling, induced by AR overexpression or 5alpha-dihydrotestosterone, suppressed VDR transactivation.
  • Specific AR coregulators, including ARA70 and ARA54, enhanced VDR transactivation.
  • Direct interaction was observed between VDR and ARA70, mediated by ARA70's LXXLL motif, which is crucial for its coactivator function.
  • Overexpression of ARA70, but not ARA54, restored VDR transactivation suppressed by AR signaling.
  • Competition for ARA70 was identified as the mechanism mediating AR's suppressive effect on VDR activity.

Conclusions:

  • AR signaling suppresses VDR transactivation, at least partly, through competition for the coactivator ARA70.
  • ARA70 acts as a critical mediator in the cross-talk between AR and VDR signaling pathways.
  • These findings provide new insights into the regulation of VDR activity by androgens and have implications for understanding hormone-driven diseases.

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