Targeting steroid receptor coactivator-1 expression with locked nucleic acids antisense reveals different thresholds for the hormonal regulation of male sexual behavior in relation to aromatase activity and protein expression

Thierry D. Charlier, Nobuhiro Harada, Gregory F. Ball, Jacques Balthazart

Research output: Contribution to journalArticle

Abstract

Steroid receptors such as the androgen and estrogen receptors require the presence of several proteins, known as coactivators, to enhance the transcription of target genes. The first goal of the present study was to define the role of SRC-1 on the steroid-dependent expression of the aromatase protein and its activity in male Japanese quail. The second goal was to analyze the rapid plasticity of the POM following antisense treatment interruption. We confirm here that the inhibition of SRC-1 expression by daily intracerebroventricular injections of locked nucleic acid antisense oligonucleotides in the third ventricle at the level of the preoptic area-hypothalamus (HPOA) significantly reduces testosterone-dependent male sexual behavior. In the first experiment, aromatase protein expression in HPOA was inhibited in SRC-1-depleted males but the enzymatic activity remained at the level measured in controls. We observed in the second experiment a recovery of the behavioral response to testosterone treatment after interruption of the antisense injection. However, several morphological characteristics of the POM were not different between the control group, the antisense-treated birds and antisense-treated birds in which treatment had been discontinued 3 days earlier. Antisense was also less effective in knocking-down SRC-1 in the present experiments as compared to our previous study. An analysis of this variation in the degree of knock-down of SRC-1 expression suggests dissociation among different aspects of steroid action on brain and behavior presumably resulting from the differential sensitivity of behavioral and neurochemical responses to the activation by testosterone and/or its estrogenic metabolites.

Original languageEnglish (US)
Pages (from-to)333-343
Number of pages11
JournalBehavioural Brain Research
Volume172
Issue number2
DOIs
StatePublished - Sep 25 2006

Fingerprint

Nuclear Receptor Coactivator 1
Aromatase
Sexual Behavior
Testosterone
Hypothalamus
Birds
Steroids
Coturnix
Injections
Proteins
Third Ventricle
Preoptic Area
Antisense Oligonucleotides
Steroid Receptors
Androgen Receptors
Estrogen Receptors
Therapeutics
Control Groups
Brain
Genes

Keywords

  • Androgen receptor
  • Aromatase
  • Estrogen receptor
  • Hypothalamus
  • Japanese quail
  • Sexual behavior
  • SRC

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Targeting steroid receptor coactivator-1 expression with locked nucleic acids antisense reveals different thresholds for the hormonal regulation of male sexual behavior in relation to aromatase activity and protein expression. / Charlier, Thierry D.; Harada, Nobuhiro; Ball, Gregory F.; Balthazart, Jacques.

In: Behavioural Brain Research, Vol. 172, No. 2, 25.09.2006, p. 333-343.

Research output: Contribution to journalArticle

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