Masculinization induced by neonatal exposure to PGE(2) or estradiol alters c-fos induction by estrous odors in adult rats.

Processing of relevant olfactory and pheromonal cues has long been known as an important process necessary for social and sexual behavior in rodents. Several nuclei that receive input from the vomeronasal projection pathway are involved in sexual behavior and show changes in immediate early gene expression after stimulation with a variety of sex-related stimuli. The nuclei in this pathway are sexually dimorphic due to the early patterning events induced by estradiol derived from testicular androgens, which developmentally defeminize and masculinize the brain and adult sexual behavior. Masculinization can be induced independently of estradiol via prostaglandin-E(2) (PGE(2)), and therefore assessed separately from defeminization. Here we examined the effects of brain defeminization and masculinization on neuronal response to sex-related odors using Fos, the protein product of the immediate early gene c-fos, as an indicator of activity. Female rat pups treated with a cyclooxygenase-2 inhibitor, to reduce PGE(2), plus estradiol, estradiol alone, and PGE(2) alone were exposed to estrous female odor as adults and the resulting Fos expression was examined in the medial amygdala, preoptic area, and ventromedial nucleus of the hypothalamus. Defeminized and/or masculinized females all showed patterns of Fos activity similar to control males and significantly different from control females. These results suggest that early exposure to estradiol and PGE(2) do not affect olfaction in females, but switch the activity pattern of sex-related nuclei in females to resemble that of males following exposure to sexually-relevant cues.