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Updated: Aug 17, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
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Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

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Receptor isoform and ligand-specific modulation of dihydrotestosterone-induced prostate specific antigen gene

Yuan-Shan Zhu1, Li-Qun Cai, Ying Huang

  • 1Department of Medicine/Endocrinology, Weill Medical College of Cornell University, 1300 York Ave, Box 149, New York, NY 10021, USA. yuz2002@med.cornell.edu

Journal of Andrology
|June 16, 2005
PubMed

Insights

Estrogens modulate androgen receptor (AR) activity in prostate cancer cells. Different estrogen receptor (ER) types and ligands show specific effects on prostate-specific antigen (PSA) gene expression and tumor cell growth.

Area of Science:

  • Molecular Endocrinology
  • Prostate Cancer Biology
  • Hormone Receptor Signaling

Background:

  • Androgens, acting through the androgen receptor (AR), are critical in prostate physiology and cancer.
  • Estrogens can either inhibit or potentiate androgen actions, but the underlying mechanisms are not fully understood.
  • Understanding these interactions is key to developing targeted prostate cancer therapies.

Purpose of the Study:

  • To investigate how estrogens modulate androgen-induced prostate-specific antigen (PSA) gene expression.
  • To examine the effects of estrogens on prostate tumor cell growth.
  • To elucidate the role of different estrogen receptor (ER) isoforms and ligands in these modulations.

Main Methods:

  • Cotransfection assays were performed in various cell lines (CV-1, DU-145, PC-3) to assess PSA transcription activity.
  • Experiments utilized different estrogen receptor isoforms (ERalpha, ERbeta) and various estrogenic ligands.
  • LAPC-4 prostate tumor cells were treated with dihydrotestosterone (DHT) and different estrogens to evaluate gene expression and cell growth.

Main Results:

  • Estrogen receptor alpha (ERalpha) mediated inhibition of DHT-induced PSA transcription by 17beta-estradiol, diethylstilbestrol, ICI182780, and 17alpha-estradiol.
  • Estrogen receptor beta (ERbeta) showed differential effects, with 17alpha-estradiol inhibiting and ICI182780/tamoxifen potentiating DHT action.
  • In prostate tumor cells (LAPC-4), DHT-induced PSA expression and cell growth were dose-dependently attenuated by 17alpha-estradiol, 17beta-estradiol, and cyproterone acetate.

Conclusions:

  • Estrogens exert ER-isoform- and ER-ligand-specific modulation of androgen signaling in prostate cells.
  • These findings provide a molecular basis for understanding estrogen's complex role in prostate cancer.
  • This knowledge can inform the design of novel therapeutic agents for prostate cancer prevention and treatment.

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