Steroid receptor coactivator 2 modulates steroid‐dependent male sexual behavior and neuroplasticity in Japanese quail (Coturnix japonica)

Abstract

Steroid receptor coactivators are necessary for efficient transcriptional regulation by ligand-bound nuclear receptors, including estrogen and androgen receptors. SRC-2 modulates estrogen- and progesterone-dependent sexual behavior in female rats but its implication in the control of male sexual behavior has not been studied to our knowledge. We cloned and sequenced the complete quail SRC-2 transcript and showed by semi-quantitative PCR that SRC-2 expression is nearly ubiquitous, with high levels of expression in the kidney, cerebellum and diencephalon. Real time quantitative PCR did not reveal any differences between intact males and females the medial preoptic nucleus (POM), optic lobes and cerebellum. We next investigated the physiological and behavioral role of this coactivator using in vivo antisense oligonucleotide (AS) techniques. Daily injections in the third ventricle at the level of the POM of locked nucleic acid antisense targeting SRC-2 significantly reduced the expression of testosterone-dependent male-typical copulatory behavior but no inhibition of one aspect of the appetitive sexual behavior was observed. The volume of POM, defined by aromatase-immunoreactive cells, was markedly decreased in animals treated with AS as compared to controls. These results demonstrate that SRC-2 plays a prominent role in the control of steroid-dependent male sexual behavior and its associated neuroplasticity in Japanese quail.

c‐fos down‐regulation inhibits testosterone‐dependent male sexual behavior and the associated learning

“…). We used chimeric oligodeoxynucleotide consisting of DNA and LNA (Charlier et al ., , ; Niessen et al ., ; Eurogentec S.A., Seraing, Belgium). The sequence for the 19‐mer AS spanning the putative start codon of the quail c‐fos was 5′‐TGGTacatcatgtcgGCTG‐3′ (the monomers are represented by uppercase letters and DNA monomers by lowercase letters), and the scrambled control oligodeoxynucleotide was 5′‐GTTGaacttcatgcgCGGT‐3′.…”

Nuclear Receptor Coactivators: Regulators of Steroid Action in Brain and Behaviour

“…In the quail brain, SRC‐1 is expressed in the steroid sensitive areas, including the POM and bed nucleus of stria terminalis . Similar to SRC‐1, quail POM expresses SRC‐2 protein in a level that is similar in males and females .…”

Modulation of testosterone-dependent male sexual behavior and the associated neuroplasticity

“…In addition, several coactivators, other than SRC-1, are very likely part of the physiological and behavioral response to T. Notably, SRC-1 is a member of the SRC family encompassing two other coactivators [104]. Its closely related member, SRC-2, shows a significant homology with SRC-1 and more importantly, exhibits the same functional domains [6, 70]. In vitro and in vivo studies indicate that SRC-2 interacts with numerous nuclear receptors, including ER and androgen receptors (AR), and dramatically enhances the transcriptional activity of these steroid receptors [51, 96, 103].…”

“…In vitro and in vivo studies indicate that SRC-2 interacts with numerous nuclear receptors, including ER and androgen receptors (AR), and dramatically enhances the transcriptional activity of these steroid receptors [51, 96, 103]. In addition, the neuroanatomical pattern of SRC-2 expression seems to match the pattern of SRC-1 expression in numerous brain regions in quail, including the POM [70], similarly to what was described in rodents [5]. Not surprisingly then, the functions of SRC-1 and -2 in the brain seem to be redundant and one coactivator seems to easily replace the other [71, 102].…”

“…Using the same methods as for SRC-1, we targeted SRC-2 expression in the POM using the antisense technique and showed that the chronic down-regulation of the coactivator expression led to a significant reduction of all consummatory aspects of male sexual behavior, including neck grabs, mount attempts, mounts (and cloacal contact movements ([70] and see figure 3D). In parallel to the copulatory behavior per se, we also analyzed the appetitive aspect of sexual behavior by comparing the mean numbers of RCSM and showed that SRC-2 depletion did not affect this form of appetitive behavior (figure 3E).…”