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Gene knock down via antisense oligonucleotides to the steroid receptor coactivator SRC-1 modulates testosterone-dependent male sexual behavior and neural gene expression
Charlier, Thierry; Ball, Gregory F; Balthazart, Jacques
2004In Hormones and Behavior, 46, p. 86
 

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Abstract :
[en] Studies of eukaryotic genome expression demonstrate the importance of steroid receptor coactivators in mediating efficient gene transcription. Little is know about the physiological role of these coactivators in vivo. We recently showed that the Steroid Receptor Coactivator SRC-1 is densely expressed in steroid-sensitive brain areas in birds and its expression is steroid-dependent and sexually differentiated. We tested the role of SRC-1 in the activation by testosterone of male sexual behavior in quail. Daily injections of LNA antisense oligonucleotides in the third ventricle (AS group) significantly reduced the expression of male copulatory behavior in response to exogenous testosterone compared to control animals (Ctrl group) receiving the vehicle alone or scrambled LNA. Sexual behavior was restored and even enhanced within 48 hours after interruption of LNA injection (ASSC group). Western blot analysis confirmed the decrease of SRC-1 expression in AS animals and suggested an over-expression of the coactivator in ASSC animals. The effect of SRC-1 knock down on behavior was correlated with a reduced volume of the medial preoptic nucleus (POM) defined by Nissl-staining and aromatase immunohistochemistry. In addition, the amount of aromatase-immunoreactive material in POM, defined as the relative optical density of the aromatase immunoreactivity multiplied by the percentage of surface covered within the nucleus and by the total POM volume of the POM, was decreased in the AS compared to the Ctrl group, suggesting a blockade of aromatase transcription. Together, these data indicate that SRC-1 functions as a critical regulatory molecule in the brain that modulates steroid-dependent gene transcription and behavior.
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Author, co-author :
Charlier, Thierry ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau
Ball, Gregory F
Balthazart, Jacques  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau
Language :
English
Title :
Gene knock down via antisense oligonucleotides to the steroid receptor coactivator SRC-1 modulates testosterone-dependent male sexual behavior and neural gene expression
Publication date :
2004
Event name :
Annual Meeting of the Society for Behavioral Neuroendocrinology
Audience :
International
Journal title :
Hormones and Behavior
ISSN :
0018-506X
eISSN :
1095-6867
Publisher :
Academic Press, San Diego, United States - California
Volume :
46
Pages :
86
Available on ORBi :
since 08 January 2010

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