Estrogen Receptor β Activation Rapidly Modulates Male Sexual Motivation through the Transactivation of Metabotropic Glutamate Receptor 1a.
Identifieur interne : 001802 ( Main/Exploration ); précédent : 001801; suivant : 001803Estrogen Receptor β Activation Rapidly Modulates Male Sexual Motivation through the Transactivation of Metabotropic Glutamate Receptor 1a.
Auteurs : Aurore L. Seredynski [Belgique] ; Jacques Balthazart [Belgique] ; Gregory F. Ball [États-Unis] ; Charlotte A. Cornil [Belgique]Source :
- The Journal of neuroscience : the official journal of the Society for Neuroscience [ 1529-2401 ] ; 2015.
Descripteurs français
- KwdFr :
- Agents des acides aminés excitateurs (pharmacologie), Analyse de variance, Animaux, Antienzymes (pharmacologie), Aromatase (métabolisme), Comportement sexuel animal (), Comportement sexuel animal (physiologie), Coturnix, Facteurs temps, Hormones (pharmacologie), Motivation (), Motivation (physiologie), Mâle, Nitriles (pharmacologie), Oestradiol (pharmacologie), Propionates (pharmacologie), Relation dose-effet des médicaments, Récepteur bêta des oestrogènes (métabolisme), Récepteurs métabotropes au glutamate (métabolisme), Triazoles (pharmacologie).
- MESH :
- métabolisme : Aromatase, Récepteur bêta des oestrogènes, Récepteurs métabotropes au glutamate.
- pharmacologie : Agents des acides aminés excitateurs, Antienzymes, Hormones, Nitriles, Oestradiol, Propionates, Triazoles.
- physiologie : Comportement sexuel animal, Motivation.
- Analyse de variance, Animaux, Comportement sexuel animal, Coturnix, Facteurs temps, Motivation, Mâle, Relation dose-effet des médicaments.
English descriptors
- KwdEn :
- Analysis of Variance, Animals, Aromatase (metabolism), Coturnix, Dose-Response Relationship, Drug, Enzyme Inhibitors (pharmacology), Estradiol (pharmacology), Estrogen Receptor beta (metabolism), Excitatory Amino Acid Agents (pharmacology), Hormones (pharmacology), Male, Motivation (drug effects), Motivation (physiology), Nitriles (pharmacology), Propionates (pharmacology), Receptors, Metabotropic Glutamate (metabolism), Sexual Behavior, Animal (drug effects), Sexual Behavior, Animal (physiology), Time Factors, Triazoles (pharmacology).
- MESH :
- chemical , metabolism : Aromatase, Estrogen Receptor beta, Receptors, Metabotropic Glutamate.
- chemical , pharmacology : Enzyme Inhibitors, Estradiol, Excitatory Amino Acid Agents, Hormones, Nitriles, Propionates, Triazoles.
- drug effects : Motivation, Sexual Behavior, Animal.
- physiology : Motivation, Sexual Behavior, Animal.
- Analysis of Variance, Animals, Coturnix, Dose-Response Relationship, Drug, Male, Time Factors.
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 targeting ERα (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. Significance statement: The membrane-associated receptors underlying the acute effects of estrogens on behavior have mostly been documented in females, where active estrogens are thought to be of ovarian origin. Using acute intracerebroventricular injections of specific agonists and antagonists following blockade of brain aromatase, we show here that brain-derived estrogens acutely facilitate male sexual motivation through the activation of estrogen receptor β interacting with the metabotropic glutamate receptor 1a. This behavioral effect occurring within minutes provides a mechanistic explanation of how an estrogen receptor not intrinsically coupled to intracellular effectors can signal from the membrane to govern behavior in a very rapid fashion. It suggests that different subtypes of estrogen receptors could regulate the motivation versus performance aspects of behavior.
DOI: 10.1523/JNEUROSCI.2056-15.2015
PubMed: 26400941
Affiliations:
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Le document en format XML
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<term>Animals</term>
<term>Aromatase (metabolism)</term>
<term>Coturnix</term>
<term>Dose-Response Relationship, Drug</term>
<term>Enzyme Inhibitors (pharmacology)</term>
<term>Estradiol (pharmacology)</term>
<term>Estrogen Receptor beta (metabolism)</term>
<term>Excitatory Amino Acid Agents (pharmacology)</term>
<term>Hormones (pharmacology)</term>
<term>Male</term>
<term>Motivation (drug effects)</term>
<term>Motivation (physiology)</term>
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<term>Propionates (pharmacology)</term>
<term>Receptors, Metabotropic Glutamate (metabolism)</term>
<term>Sexual Behavior, Animal (drug effects)</term>
<term>Sexual Behavior, Animal (physiology)</term>
<term>Time Factors</term>
<term>Triazoles (pharmacology)</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Agents des acides aminés excitateurs (pharmacologie)</term>
<term>Analyse de variance</term>
<term>Animaux</term>
<term>Antienzymes (pharmacologie)</term>
<term>Aromatase (métabolisme)</term>
<term>Comportement sexuel animal ()</term>
<term>Comportement sexuel animal (physiologie)</term>
<term>Coturnix</term>
<term>Facteurs temps</term>
<term>Hormones (pharmacologie)</term>
<term>Motivation ()</term>
<term>Motivation (physiologie)</term>
<term>Mâle</term>
<term>Nitriles (pharmacologie)</term>
<term>Oestradiol (pharmacologie)</term>
<term>Propionates (pharmacologie)</term>
<term>Relation dose-effet des médicaments</term>
<term>Récepteur bêta des oestrogènes (métabolisme)</term>
<term>Récepteurs métabotropes au glutamate (métabolisme)</term>
<term>Triazoles (pharmacologie)</term>
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<term>Estrogen Receptor beta</term>
<term>Receptors, Metabotropic Glutamate</term>
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<term>Excitatory Amino Acid Agents</term>
<term>Hormones</term>
<term>Nitriles</term>
<term>Propionates</term>
<term>Triazoles</term>
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<term>Récepteurs métabotropes au glutamate</term>
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<term>Nitriles</term>
<term>Oestradiol</term>
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<front><div type="abstract" xml:lang="en">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 targeting ERα (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. Significance statement: The membrane-associated receptors underlying the acute effects of estrogens on behavior have mostly been documented in females, where active estrogens are thought to be of ovarian origin. Using acute intracerebroventricular injections of specific agonists and antagonists following blockade of brain aromatase, we show here that brain-derived estrogens acutely facilitate male sexual motivation through the activation of estrogen receptor β interacting with the metabotropic glutamate receptor 1a. This behavioral effect occurring within minutes provides a mechanistic explanation of how an estrogen receptor not intrinsically coupled to intracellular effectors can signal from the membrane to govern behavior in a very rapid fashion. It suggests that different subtypes of estrogen receptors could regulate the motivation versus performance aspects of behavior.</div>
</front>
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