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Isolation of Targeted Hypothalamic Neurons for Studies of Hormonal, Metabolic, and Electrical Regulation
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Isolation of Targeted Hypothalamic Neurons for Studies of Hormonal, Metabolic, and Electrical Regulation

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Estrogen receptor alpha is expressed on the cell-surface of embryonic hypothalamic neurons

S V Gorosito1, A G Lorenzo, M J Cambiasso

  • 1Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET, Córdoba, Argentina.

Neuroscience
|June 17, 2008
PubMed

Insights

Estrogen

Area of Science:

  • Neuroendocrinology
  • Molecular Endocrinology
  • Cell Biology

Background:

  • Estrogen's biological activity is primarily mediated by nuclear estrogen receptors (ER).
  • Rapid, non-genomic effects suggest the involvement of membrane estrogen receptors (mER).
  • The precise nature and location of mER responsible for these rapid effects remain elusive.

Purpose of the Study:

  • To investigate the presence and localization of estrogen receptor alpha (ERalpha) at the plasma membrane.
  • To determine if ERalpha at the cell surface mediates rapid signaling pathways.

Main Methods:

  • Subcellular fractionation of rat hypothalamic tissue at embryonic day 16.
  • Cell surface biotinylation of rat hypothalamic neurons in vitro.
  • Detection of ERalpha expression in plasma membrane fractions.
  • Analysis of extracellular-signal-regulated kinase (ERK) signaling pathway activation.

Main Results:

  • ERalpha expression was detected in the plasma membrane fraction of embryonic rat hypothalamus.
  • ERalpha was identified as a cell-surface protein on hypothalamic neurons, accessible from the cell exterior.
  • Estradiol regulates mERalpha expression.
  • An ERalpha agonist rapidly induced ERK signaling in a dose- and time-dependent manner, inconsistent with genomic effects.

Conclusions:

  • ERalpha is expressed at the plasma membrane of hypothalamic neurons.
  • ERalpha functions as a membrane estrogen receptor (mERalpha) mediating rapid, non-genomic signaling.
  • These findings support a role for membrane-initiated estrogen signaling in the hypothalamus.

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