Sex Hormonal Modulation of Neural Development in Vitro: Implications for Brain Sex Differentiation
Robert H. Lustig
Most animal species which undergo sexual reproduction, whether invertebrate or vertebrate, have evolved such that the two sexes of the species are easily discernable. This is true for general appearance, external and internal sexual organs, and how the two sexes behave, both in general (cognitive behavior), and toward each other (reproductive behavior). Much study on sex differences in behavior has taken place over the past century, in particular in the past twenty-five years. Recently, specific sex differences in brain structure have been elucidated. However, the biologic causes of these sex differences remain elusive. It appears that factors such as genes, hormones, and environmental cues all play roles in brain sex dimorphisms. This chapter will focus on the role of sex hormones in brain development, and their implications for brain sex differentiation.
Studies on neuroanatomic sex differentiation thus far have been descriptive and inferring causation based on in vivo sex differences. Our lab has instead attempted to define specific cellular effects of sex hormones on neurons to directly examine causation. Though the details of this chapter focus on in vitro models of sex hormones on neurons rather than whole animal phenomena, and though these models come from rodent cells, it is this author's belief that these phenomena are likely transferable to other species, including humans. In this chapter, a molecular/cellular hypothesis of neuroanatomic brain sex differentiation is offered, and the reader is invited to compare these principles to their own models or paradigms to determine the universality of this hypothesis.