Estrogen receptor β activation rapidly modulates male sexual motivation through the transactivation of metabotropic glutamate receptor 1a

Aurore L. Seredynski, Jacques Balthazart, Gregory F. Ball, Charlotte A. Cornil

Research output: Contribution to journalArticle

Abstract

In addition to the transcriptional activity of their liganded nuclear receptors, estrogens, such as estradiol (E2), modulate cell functions, and consequently physiology and behavior, within minutes through membrane-initiated events. The membrane-associated receptors (mERs) underlying the acute effects of estrogens on behavior have mostly been documented in females where active estrogens are thought to be of ovarian origin. We determined here, by acute intracerebroventricular injections of specific agonists and antagonists, the type(s) of mERs that modulate rapid effects of brain-derived estrogens on sexual motivation in male Japanese quail. Brain aromatase blockade acutely inhibited sexual motivation. Diarylpropionitrile (DPN), an estrogen receptor β (ERβ)-specific agonist, and to a lesser extent 17α -estradiol, possibly acting through ER-X, prevented this effect. In contrast, drugs targetingERα (PPT and MPP), GPR30 (G1 and G15), and the Gq-mER (STX) did not affect sexual motivation. The mGluR1a antagonist LY367385 significantly inhibited sexual motivation but mGluR2/3 and mGluR5 antagonists were ineffective. LY367385 also blocked the behavioral restoration induced by E2 or DPN, providing functional evidence that ERβ interacts with metabotropic glutamate receptor 1a (mGluR1a) signaling to acutely regulate male sexual motivation. Together these results show that ERβ plays a key role in sexual behavior regulation and the recently uncovered cooperation between mERs and mGluRs is functional in males where it mediates the acute effects of estrogens produced centrally in response to social stimuli. The presence of an ER–mGluR interaction in birds suggests that this mechanism emerged relatively early in vertebrate history and is well conserved.

Original languageEnglish (US)
Pages (from-to)13110-13123
Number of pages14
JournalJournal of Neuroscience
Volume35
Issue number38
DOIs
StatePublished - Sep 23 2015
Externally publishedYes

Fingerprint

Metabotropic Glutamate Receptors
Estrogen Receptors
Transcriptional Activation
Motivation
Estrogens
alpha-methyl-4-carboxyphenylglycine
Membranes
Estradiol
Coturnix
Excitatory Amino Acid Antagonists
Aromatase
Brain
Sexual Behavior
Birds
Vertebrates
History
Injections
Pharmaceutical Preparations

Keywords

  • ERβ
  • Estrogens
  • Membrane-initiated effects
  • Sexual motivation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Estrogen receptor β activation rapidly modulates male sexual motivation through the transactivation of metabotropic glutamate receptor 1a. / Seredynski, Aurore L.; Balthazart, Jacques; Ball, Gregory F.; Cornil, Charlotte A.

In: Journal of Neuroscience, Vol. 35, No. 38, 23.09.2015, p. 13110-13123.

Research output: Contribution to journalArticle

Seredynski, Aurore L. ; Balthazart, Jacques ; Ball, Gregory F. ; Cornil, Charlotte A. / Estrogen receptor β activation rapidly modulates male sexual motivation through the transactivation of metabotropic glutamate receptor 1a. In: Journal of Neuroscience. 2015 ; Vol. 35, No. 38. pp. 13110-13123.
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