Sex difference and testosterone modulation of pheromone-induced neuronal Fos in the ferret's main olfactory bulb and hypothalamus

A carnivore, the ferret possesses a vomeronasal organ-accessory olfactory b ulb (VNO-AOB) projection to the hypothalamus; however, little is known abou t its function. Pheromones in soiled bedding from estrous female ferrets or an artificial peppermint odor significantly augmented nuclear Fos protein immunoreactivity (Fos-IR), a marker of neural activation, in several main o lfactory bulb (MOB) sites but not in the AOB of gonadectomized male and fem ales. Testosterone propionate (TP) significantly augmented the MOB's neuron al Fos responses to estrous females' pheromones, but not to peppermint. Est rous odors, but not peppermint, also augmented neuronal Fos-IR in the media l preoptic area (mPOA) of female, but not male, subjects. Pheromones in soi led bedding from breeding male ferrets significantly augmented neuronal Fos -IR in the MOB and in the medial amygdala of gonadectomized, TP-treated mal e and female subjects. Again, male pheromones failed to influence neuronal Fos-IR in the AOB of either sex, and only females showed significant increa ses in neuronal Fos-IR in the lateral aspect of the ventromedial nucleus an d mPOA, These results point to an essential role among higher mammals of th e main olfactory epithelium-MOB projection to the hypothalamus in detecting and processing pheromones. Gonadectomized ferrets showed significant incre ases in sniffing behavior when placed on either female or male bedding. Thi s occurred regardless of whether they had received TP or oil vehicle, sugge sting that testosterone's facilitation of neuronal Fos responses to estrous females' odors in the MOB of both sexes cannot be attributed to increased scent gathering. Androgen receptor-IR was present in the MOB granule cell l ayer of male and female ferrets, raising the possibility that testosterone acts directly on these cells to augment their responsiveness to pheromones.