Sex and gonadal steroid modulation of pheromone receptor gene expression in the mouse vomeronasal organ

Non-volatile chemosignals in rodents are detected by unique receptors in the vomeronasal organ of the accessory olfactory system. Although the vomeronasal organ has been implicated in the regulation of sexually dimorphic behavioral and neuroendocrine functions, the underlying cellular mechanisms are undetermined. In previous studies we showed that exposure to soiled male bedding augmented immediate early gene immunoreactivity in neurons of the basal zone of the vomeronasal organ, an effect that depended on gender and sex steroid expression. To determine whether this effect could be due to differences in vomeronasal organ receptor expression, we examined two representatives (VR1 and VR4) from different subfamilies of the V2R family of receptors that are expressed in the basal zone of the vomeronasal organ. Adult Swiss-Webster male and female mice were gonadectomized and implanted with capsules containing 17β-estradiol, testosterone or neither steroid (control). Two weeks later vomeronasal organs were processed for in situ hybridization using probes from the N-terminal extracellular domains of VR1 and VR4. Expression of both VR1 and VR4 was significantly higher in males than in females. Estradiol, but not testosterone-treated, males had significantly lower levels of VR1 expression in the caudal vomeronasal organ compared with untreated gonadectomized males. In contrast, testosterone enhanced VR4 expression in males relative to similarly treated females. Despite these effects, we found no evidence that vomeronasal organ neurons express either androgen or estrogen receptors. These data show that expression of vomeronasal organ receptors in mice is sexually dimorphic and regulated by sex steroids. Thus, gonadal hormones may affect the response of vomeronasal organ neurons to chemosignals by altering levels of the receptors to which they bind.