aromatase; estetrol; estrogen receptor alpha; neuroestrogens; sexual behavior; Estradiol; Estrogen Receptor alpha; Estrogens; Receptors, Estrogen; Animals; Female; Male; Mice; Estradiol/metabolism; Motivation; Estrogen Receptor alpha/genetics; Sexual Behavior, Animal; Endocrinology, Diabetes and Metabolism; Endocrinology; Endocrine and Autonomic Systems; Cellular and Molecular Neuroscience
Abstract :
[en] The activation of male sexual behavior depends on brain estrogen synthesis. Estrogens act through nuclear and membrane receptors producing effects within hours/days or seconds/minutes, respectively. In mice, estrogen receptor alpha (ERα) is the main estrogen receptor (ER) controlling the activation of male sexual behavior. Although neuroestrogens rapidly modulate mouse sexual behavior, it is not known whether these effects involve membrane ERα (mERα). This study combines two complementary approaches to address this question. C451A-ERα mice carry an ERα that cannot signal at the membrane, while estetrol (E4) is a natural estrogen acting as an agonist on nuclear ERα but as an antagonist on membrane ERα. In wild-type males, E4 decreased the number of mounts and intromissions after 10 min. In C451A-ERα males, E4 also altered sexual performance but after 30 min. E4 did not affect time spent near the female in both wild-type and C451A-ERα mice. However, regardless of genotype, the aromatase inhibitor 1,4,6-Androstatriene-3,17-dione (ATD) decreased both sexual performance and the time spent near the female after 10 and 30 min, confirming the key role of aromatization in the rapid control of sexual behavior and motivation. In conclusion, the shift in timing at which the effect of E4 is observed in mice lacking mERα suggests a role for mERα in the regulation of rapid effects of neuroestrogens on sexual performance, thus providing the first demonstration that E4 acts as an antagonist of a mER in the brain. The persisting effect of ATD on behavior in C451A-ERα mice also suggests the implication of another ER.
Research center :
GIGA Neurosciences-Neuroendocrinology - ULiège
Disciplines :
Neurosciences & behavior
Author, co-author :
de Bournonville, Catherine; Laboratory of Neuroendocrinology, GIGA Neurosciences, University of Liège, Liège, Belgium
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques ; Estetra SRL, an affiliate company of Mithra Pharmaceuticals, Liège, Belgium
Arnal, Jean-François; Institute of Metabolic and Cardiovascular Diseases (I2MC) Equipe 4, Inserm U1297-UPS, CHU, Toulouse, France
Lenfant, Françoise; Institute of Metabolic and Cardiovascular Diseases (I2MC) Equipe 4, Inserm U1297-UPS, CHU, Toulouse, France
Cornil, Charlotte ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Language :
English
Title :
Role of membrane estrogen receptor alpha (ERα) in the rapid regulation of male sexual behavior.
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Funding text :
This work was supported by grants from the Fonds National pour la Recherche Scientifique (F.R.S.‐FNRS PDR T.0042.15 to CAC) and the Fondation Léon Frédéricq (to CdB). Catherine de Bournonville was a Post‐doctoral Researcher of the F.R.S.‐FNRS, Philippine Lemoine is a PhD student of the F.R.S.‐FNRS and Charlotte A. Cornil is a Research Director of the F.R.S.‐FNRS.
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