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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 16, 2013

Selective modulation of genomic and nongenomic androgen responses by androgen receptor ligands

Lindsey B Lutz1, Michelle Jamnongjit, Wei-Hsiung Yang

  • 1Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-8857, USA.

Molecular Endocrinology (Baltimore, Md.)
|March 15, 2003
PubMed

Insights

Androgen receptor (AR) ligands trigger genomic and nongenomic signaling. In Xenopus oocytes, the oocyte-expressed AR mediates transcription-independent maturation, highlighting ligand and cell-type specific responses.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Biology

Background:

  • Steroids elicit both genomic (transcription-dependent) and nongenomic (transcription-independent) signaling pathways.
  • The androgen receptor (AR) plays a key role in mediating cellular responses to androgens.
  • Understanding the differential modulation of these pathways is crucial for comprehending androgen action.

Purpose of the Study:

  • To investigate the ability of classical androgen receptor ligands to modulate genomic and nongenomic responses.
  • To elucidate the role of the oocyte-expressed Xenopus classical androgen receptor (XeAR) in mediating these processes.
  • To determine how ligand type and cell context influence AR signaling.

Main Methods:

  • Utilized cellular fractionation and immunohistochemistry to determine XeAR localization.
  • Employed RNA interference and oocyte maturation assays to assess androgen-induced signaling.
  • Compared XeAR-mediated transcription in oocytes versus CV1 cells following ligand treatment.

Main Results:

  • XeAR was found throughout oocytes, including the plasma membrane.
  • Androgen-induced oocyte maturation was partially mediated by XeAR in a transcription-independent manner.
  • Testosterone and androstenedione induced maturation, while other ligands inhibited it; ligand-specific transcription varied between cell types.

Conclusions:

  • The nature of steroid-induced signaling (genomic vs. nongenomic) is dependent on the target cell, receptor localization, and the specific ligand.
  • XeAR mediates transcription-independent signaling in oocytes, potentially involving G protein pathways.
  • Selective modulation of genomic and nongenomic pathways offers potential for developing novel therapeutic compounds.

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