12. Sex and brain development

Abstract

Consistent with the importance of reproductive behavior for survival of the species, the gonadal steroids are major regulators of neural function and brain development. Investigation of these regulatory effects has revealed both mechanisms and principles that underlie emergent behavioral properties. First, activational effects of gonadal steroids comprise both acute, signal transduction-mediated and classical, intracellular receptor-mediated actions, the latter including modulation of the synthesis of the synthetic and metabolic enzymes for neurotransmitters, neuropeptides, neuroeffector receptors, and second messengers. Second, gonadal steroids create a context that influences both formation of neurocircuitry and acute neural response. These actions are largely inferred from three types of observations: structural and functional sexual dimorphisms; changes in neural response during reproductive endocrine change (e.g. the ovulatory cycle); and modulation of response to hormone manipulation (e.g. castration). In fact, all stages of neuronal development—neurogenesis, growth, migration, differentiation, and synaptic organization—are modulated by gonadal steroids. Third, gonadal steroids organize the brain during critical developmental windows. Androgen blockade, for example, alters 5-HT1A receptor m-RNA but not GABA receptor subunit expression during the last prenatal week, while the opposite is observed during the fourth postnatal week. Fourth, the effects of gonadal steroids are context dependent and differ as a function of environment, prior exposure, age, and genotypic characteristics. Studies of the effects of gonadal steroids on behavior promise to help answer the critical question in human behavioral endocrinology: Why do different individuals respond differently to ostensibly the same stimulus?