Visualising androgen receptor activity in male and female mice.

Androgens, required for normal development and fertility of males and females, have vital roles in the reproductive tract, brain, cardiovascular system, smooth muscle and bone. Androgens function via the androgen receptor (AR), a ligand-dependent transcription factor. To assay and localise AR activi...

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Main Authors: D Alwyn Dart, Jonathan Waxman, Eric O Aboagye, Charlotte L Bevan
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3737126?pdf=render
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author D Alwyn Dart
Jonathan Waxman
Eric O Aboagye
Charlotte L Bevan
author_facet D Alwyn Dart
Jonathan Waxman
Eric O Aboagye
Charlotte L Bevan
author_sort D Alwyn Dart
collection DOAJ
description Androgens, required for normal development and fertility of males and females, have vital roles in the reproductive tract, brain, cardiovascular system, smooth muscle and bone. Androgens function via the androgen receptor (AR), a ligand-dependent transcription factor. To assay and localise AR activity in vivo we generated the transgenic "ARE-Luc" mouse, expressing a luciferase reporter gene under the control of activated endogenous AR. In vivo imaging of androgen-mediated luciferase activity revealed several strongly expressing tissues in the male mouse as expected and also in certain female tissues. In males the testes, prostate, seminal vesicles and bone marrow all showed high AR activity. In females, strong activity was seen in the ovaries, uterus, omentum tissue and mammary glands. In both sexes AR expression and activity was also found in salivary glands, the eye (and associated glands), adipose tissue, spleen and, notably, regions of the brain. Luciferase protein expression was found in the same cell layers as androgen receptor expression. Additionally, mouse AR expression and activity correlated well with AR expression in human tissues. The anti-androgen bicalutamide reduced luciferase signal in all tissues. Our model demonstrates that androgens can act in these tissues directly via AR, rather than exclusively via androgen aromatisation to estrogens and activation of the estrogen receptor. Additionally, it visually demonstrates the fundamental importance of AR signalling outside the normal role in the reproductive organs. This model represents an important tool for physiological and developmental analysis of androgen signalling, and for characterization of known and novel androgenic or antiandrogenic compounds.
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spelling doaj.art-d0d199d8a77c4f63b7527228ba59d93d2022-12-21T23:20:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7169410.1371/journal.pone.0071694Visualising androgen receptor activity in male and female mice.D Alwyn DartJonathan WaxmanEric O AboagyeCharlotte L BevanAndrogens, required for normal development and fertility of males and females, have vital roles in the reproductive tract, brain, cardiovascular system, smooth muscle and bone. Androgens function via the androgen receptor (AR), a ligand-dependent transcription factor. To assay and localise AR activity in vivo we generated the transgenic "ARE-Luc" mouse, expressing a luciferase reporter gene under the control of activated endogenous AR. In vivo imaging of androgen-mediated luciferase activity revealed several strongly expressing tissues in the male mouse as expected and also in certain female tissues. In males the testes, prostate, seminal vesicles and bone marrow all showed high AR activity. In females, strong activity was seen in the ovaries, uterus, omentum tissue and mammary glands. In both sexes AR expression and activity was also found in salivary glands, the eye (and associated glands), adipose tissue, spleen and, notably, regions of the brain. Luciferase protein expression was found in the same cell layers as androgen receptor expression. Additionally, mouse AR expression and activity correlated well with AR expression in human tissues. The anti-androgen bicalutamide reduced luciferase signal in all tissues. Our model demonstrates that androgens can act in these tissues directly via AR, rather than exclusively via androgen aromatisation to estrogens and activation of the estrogen receptor. Additionally, it visually demonstrates the fundamental importance of AR signalling outside the normal role in the reproductive organs. This model represents an important tool for physiological and developmental analysis of androgen signalling, and for characterization of known and novel androgenic or antiandrogenic compounds.http://europepmc.org/articles/PMC3737126?pdf=render
spellingShingle D Alwyn Dart
Jonathan Waxman
Eric O Aboagye
Charlotte L Bevan
Visualising androgen receptor activity in male and female mice.
PLoS ONE
title Visualising androgen receptor activity in male and female mice.
title_full Visualising androgen receptor activity in male and female mice.
title_fullStr Visualising androgen receptor activity in male and female mice.
title_full_unstemmed Visualising androgen receptor activity in male and female mice.
title_short Visualising androgen receptor activity in male and female mice.
title_sort visualising androgen receptor activity in male and female mice
url http://europepmc.org/articles/PMC3737126?pdf=render
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