Previously [D.W. Wesson, M. Keller, Q. Douhard, M.J. Baum, J. Bakker, Enhanced urinary odor discrimination in female aromatase knockout mice, Horm. Behav. 49 (2006) [580][581][582][583][584][585][586] female aromatase knock out mice successfully learned to discriminate in a food-motivated go/no-go task between urinary volatiles from ovariectomized female mice treated with estradiol as opposed to estradiol plus progesterone whereas wild type females failed to learn this odor discrimination. We asked whether this behavioral difference is reflected in the ability of these two types of urinary volatiles to differentially stimulate Fos expression in juxtaglomerular cells (an index of glomerular activation) of the main olfactory bulb (MOB) in wild type versus ArKO female mice. Statistically significant differences in the profiles of MOB glomerular activation were seen in ovariectomized, estrogen-treated ArKO as well as WT female subjects following exposure to urinary volatiles from ovariectomized females given estradiol alone as opposed to estradiol plus progesterone. Therefore, previously observed differences between females of the two genotypes in their behavioral responses to these odors must reflect differential processing in more central segments of the olfactory pathway instead of in the MOB. © 2007 Elsevier Ireland Ltd. All rights reserved.Keywords: Estradiol; Progesterone; Pheromone; Sexual differentiation; Fos expression Olfactory receptor neurons in the main olfactory epithelium (MOE) that express the same olfactory receptor gene extend axons that target the same 1-2 glomeruli in the ipsilateral main olfactory bulb (MOB) [10]. Recently [6] a class of 'trace amineassociated receptors' was identified in the MOE which respond to volatile amines emitted from mouse urine. A series of studies by Restrepo and co-workers [13,12,7] showed that volatile urinary odors from male mice augmented Fos expression in juxtaglomerular cells of the MOB (an index of glomerular activation) of female conspecifics. More recently, Martel and Baum [9] used this same method to show that urinary volatiles from male versus estrous female mice activated overlapping, but distinguishable clusters of glomeruli located in the ventral portion of the MOB in both sexes. In another study [8] volatile constituents of mouse urine were shown to stimulate activity in MOB mitral cells. Wesson et al. [14] recently assessed the possible contribution of perinatal exposure to estradiol on the later ability of female mice to discriminate volatile urinary odors from * Corresponding author. conspecifics of different sexes and endocrine status. Detection of these social odorants plays a significant role in sexual, aggressive, and maternal behaviors in mice, therefore the possible role of perinatal estradiol exposure on the later ability of female mice to discriminate between urinary odors of conspecifics is of particular interest. Female mice with a null mutation of the Cyp-19 gene (ArKO mice), which encodes the estradiol synthesizing enzyme, aroma...