Permanence of brain sex differences and structural plasticity of the adult brain.

Sex differences in brain structure have been widely recognized since the pioneering studies of Raisman and Field (1). For the most part, brain sex differences are thought to arise in perinatal development through the actions of testosterone secreted by the developing testes, and these sex differences are believed to persist in the absence of gonadal hormones in adult life, very much like the basic plan of the male and female reproductive tracts, which are also developmentally determined. As shown in Fig. 1, the basic plan of brain and body sex differences is the result of a cascade of events beginning with the role of the sex-determining genes in sexual differentiation and continuing with the actions of hormones in embryonic, neonatal, peripubertal, and adult life. The emphasis on early developmental programming of brain structural sex differences was reinforced over several decades by the long-standing view that the brain is not capable of significant structural changes in adulthood. However, this view is changing, and in this issue of the Proceedings, Cooke et al. (2) describe a brain sex difference controlled entirely by circulating androgens. The postereodorsal nucleus of the medial amygdala is larger in male rats and females, but castration of adult males causes the volume of the nucleus to decrease to female levels within 4 weeks, whereas testosterone treatment of adult females for 4 weeks enlarges volume of this nucleus to male levels. Not only is the volume of the anatomical nucleus affected, but the individual cell soma areas are also increased in size by androgen, irrespective of genetic sex of the animal. These interesting findings are not as heretical as they might have seemed a few years ago, and they should be interpreted in light of new evidence for the structural plasticity of the adult brain at different …