Ward and Weisz41,42

demonstrated that male offspring of a rat dam stressed during gestation were demasculinized, with lower testosterone levels (on critical gestational days) and deficient adult male mating behavior.43 Moore et al44 observed that the size of the sexually dimorphic spinal nucleus of the bulbocavernosus as well as adult male mating behavior were in part determined by maternal licking of the anogenital region of the pup, which in turn appeared to be elicited by androgens in the rat pup urine. Finally, reproductive hormones interact with environmental factors during development to determine the adult behavioral repertoire. Adult aggressive behavior in Inhibitors,research,lifescience,medical mice can Inhibitors,research,lifescience,medical be attenuated by prepubertal castration; the attenuation, however, is blunted to the extent to which the mouse has already been exposed to aggressive encounters.45 ‘ITticse examples demonstrate that current

and past environments and experience can create a context in which the same hormonal or environmental stimulus may elicit any of a range of behavioral responses. Gender context Early hypotheses that the brain displays sex-related differences in structure and function were confirmed by the demonstrations by Pfaff46 of sexual dimorphisms in rat brain morphology and by Raisman and Field47 of sexrelated Inhibitors,research,lifescience,medical differences in the synaptic density of the preoptic area in the rat. There is now an impressive literature detailing sexual dimorphisms at all levels of the neuroaxis, Inhibitors,research,lifescience,medical including differences in the following: nuclear volume; SAHA HDAC supplier neuron number, size, density, morphology, and gene expression; signal transduction; neuronal neuritic branching patterns;

synapse formation; and physiological and behavioral response.48,49 Given the ability of reproductive steroids to regulate virtually all stages of brain development from neurogenesis to neural migration, differentiation, synaptogenesis, survival, and death,49 the wide range of brain dimorphisms is not surprising. Nonetheless, the source and significance Inhibitors,research,lifescience,medical of many of the dimorphisms are far from clear. For example, while exposure to reproductive steroids is believed to organize (perinatally) or activate (adulthood) most dimorphisms, Reiscrt and Pilgrim50 showed that dimorphisms in the course of development of embryonic mesencephalic and diencephalic neurons appear under genetic control (ie, they are determined well before the appearance Mephenoxalone of any differences in reproductive steroid levels). Similarly, both the morphologic (eg, neuritic extension) and functional (eg, signal transduction) responses of cultured neurons and glia to reproductive steroids have been shown to display dramatic sexual dimorphisms despite exposure to identical levels of steroid,17,51,52 ie, the dimorphic response cannot be attributed to differences in the steroid milieu of males and females.