Characterization of Aromatase Expression in the Adult Male and Female Mouse Brain. I. Coexistence With Oestrogen Receptors α and β, and Androgen Receptors

PLoS One. 2014 Mar 19;9(3):e90451. doi: 10.1371/journal.pone.0090451. eCollection 2014.

Abstract

Aromatase catalyses the last step of oestrogen synthesis. There is growing evidence that local oestrogens influence many brain regions to modulate brain development and behaviour. We examined, by immunohistochemistry, the expression of aromatase in the adult male and female mouse brain, using mice in which enhanced green fluorescent protein (EGFP) is transcribed following the physiological activation of the Cyp19A1 gene. EGFP-immunoreactive processes were distributed in many brain regions, including the bed nucleus of the stria terminalis, olfactory tubercle, medial amygdaloid nucleus and medial preoptic area, with the densest distributions of EGFP-positive cell bodies in the bed nucleus and medial amygdala. Differences between male and female mice were apparent, with the density of EGFP-positive cell bodies and fibres being lower in some brain regions of female mice, including the bed nucleus and medial amygdala. EGFP-positive cell bodies in the bed nucleus, lateral septum, medial amygdala and hypothalamus co-expressed oestrogen receptor (ER) α and β, or the androgen receptor (AR), although single-labelled EGFP-positive cells were also identified. Additionally, single-labelled ERα-, ERβ- or AR-positive cell bodies often appeared to be surrounded by EGFP-immunoreactive nerve fibres/terminals. The widespread distribution of EGFP-positive cell bodies and fibres suggests that aromatase signalling is common in the mouse brain, and that locally synthesised brain oestrogens could mediate biological effects by activating pre- and post-synaptic oestrogen α and β receptors, and androgen receptors. The higher number of EGFP-positive cells in male mice may indicate that the autocrine and paracrine effects of oestrogens are more prominent in males than females.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aromatase / genetics*
  • Aromatase / metabolism
  • Brain / anatomy & histology
  • Brain / metabolism*
  • Brain Mapping
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / genetics*
  • Estrogen Receptor beta / metabolism
  • Female
  • Gene Expression Regulation*
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism
  • Sex Factors
  • Signal Transduction
  • Transcription, Genetic

Substances

  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Receptors, Androgen
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Aromatase

Grant support

This study was supported by the National Health and Medical Research Council of Australia, Project grant (ID: 628553). Victorian Government through the Operational Infrastructure Scheme. M.K.H. supported by a National Health and Medical Research Council of Australia, Australia Practitioner Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.