Reference : Inhibition of steroid receptor coactivator-1 blocks estrogen and androgen action on m...
Scientific journals : Article
Social & behavioral sciences, psychology : Neurosciences & behavior
http://hdl.handle.net/2268/11620
Inhibition of steroid receptor coactivator-1 blocks estrogen and androgen action on male sex behavior and associated brain plasticity.
English
Charlier, Thierry mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau >]
Ball, Gregory F [> > > >]
Balthazart, Jacques mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau >]
2005
Journal of Neuroscience
Society for Neuroscience
25
4
906-13
Yes (verified by ORBi)
International
0270-6474
1529-2401
Washington
DC
[en] Androgen Antagonists ; Androgens/physiology ; aromatase ; sexually dimorphic nucleus ; Japanese quail ; antisense ; vasotocin ; Animals ; Aromatase/metabolism ; Brain/metabolism/pathology/physiology ; Coturnix ; Estrogen Antagonists ; Estrogens/physiology ; Histone Acetyltransferases ; Male ; Neuronal Plasticity/physiology ; Oligodeoxyribonucleotides, Antisense ; Preoptic Area/physiology ; Sexual Behavior, Animal/physiology ; Testosterone/antagonists & inhibitors/physiology ; Transcription Factors/antagonists & inhibitors/physiology
[en] Studies of eukaryotic gene expression demonstrate the importance of nuclear steroid receptor coactivators in mediating efficient gene transcription. However, little is known about the physiological role of these coactivators in vivo. In Japanese quail, the steroid receptor coactivator-1 (SRC-1) is broadly expressed in steroid-sensitive brain areas that control the expression of male copulatory behavior, and we investigated the role of this coactivator by antisense technology. Daily intracerebroventricular injections of locked nucleic acid (LNA) antisense (AS) oligonucleotides targeting SRC-1 significantly reduced the expression of androgen- and estrogen-dependent male-typical sexual behaviors compared with control animals that received the vehicle alone or scrambled oligonucleotides. Sexual behavior was restored and even enhanced within 48 h after interruption of LNA injections. Western blot analysis confirmed the decrease of SRC-1 expression in AS animals and suggested an overexpression 48 h after the end of injections. The effects of SRC-1 knock-down on behavior correlated with a reduction in volume of the preoptic medial nucleus (POM) when its borders were defined by Nissl staining or by aromatase immunohistochemistry. The amount of aromatase-immunoreactive material in POM was also reduced in the AS compared with the control group. Previous work on SRC-1 knock-out mice raised questions about the importance of this specific coactivator in the regulation of reproductive behavior and development of sexually dimorphic structures in the CNS. Together, the present findings indicate that SRC-1 modulates steroid-dependent gene transcription and behavior and highlight the rapid time course of steroid-induced brain plasticity in adult quail.
http://hdl.handle.net/2268/11620
also: http://hdl.handle.net/2268/13902
10.1523/JNEUROSCI.3533-04.2005

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