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Updated: Mar 21, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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NF-κB and androgen receptor variant 7 induce expression of SRD5A isoforms and confer 5ARI resistance

David C Austin1, Douglas W Strand2, Harold L Love2

  • 1Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee.

The Prostate
|May 21, 2016
PubMed
Abstract

Insights

Benign prostatic hyperplasia (BPH) treatment failure may be linked to NF-κB activation and increased SRD5A2 expression. This mechanism explains why 5α-reductase inhibitors (5ARI) are less effective in some BPH patients.

Area of Science:

  • Urology
  • Molecular Biology
  • Oncology

Background:

  • Benign prostatic hyperplasia (BPH) is commonly treated with 5α-reductase inhibitors (5ARI).
  • These drugs inhibit testosterone to dihydrotestosterone conversion, leading to prostate shrinkage.
  • Treatment failure is common, particularly in inflamed prostates, often necessitating surgery.

Purpose of the Study:

  • To investigate the link between NF-κB activation and SRD5A2 expression in BPH.
  • To elucidate a potential mechanism for 5ARI therapy failure in BPH patients.

Main Methods:

  • Analysis of tissue from BPH and prostate cancer patients.
  • Genetic modification of human prostatic cell lines to regulate NF-κB, AR-FL, and AR-V7.
  • Assessment of SRD5A2 expression, androgen synthesis, and cellular response to testosterone.

Main Results:

  • SRD5A2 was upregulated in advanced BPH and associated with prostate volume and lower urinary tract symptoms.
  • NF-κB activation led to increased androgen synthesis and SRD5A2 expression.
  • Knockdown of SRD5A2 reduced cell proliferation and response to testosterone.

Conclusions:

  • Increased BPH severity correlates with SRD5A2 expression.
  • NF-κB and AR-V7 upregulate SRD5A expression, explaining 5ARI therapy failure in BPH.
  • Findings provide a molecular mechanism for treatment resistance in BPH.
Keywords:
BPHandrogen receptorandrogen receptor variant 7inflammationp65

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