DHEA effects on brain and behavior: Insights from comparative studies of aggression

• We review the essential roles of DHEA in the regulation of aggression, an important social behavior.
• We integrate studies of songbirds, rodents, non-human primates, and humans.
• Songbirds and hamsters are excellent small animal models for studying the functions of DHEA.
• The brain is an important target of DHEA.

Historically, research on the neuroendocrinology of aggression has been dominated by the paradigm that the brain receives sex steroid hormones, such as testosterone (T), from the gonads, and then these gonadal hormones modulate behaviorally relevant neural circuits. While this paradigm has been extremely useful for advancing the field, recent studies reveal important alternatives. For example, most vertebrate species are seasonal breeders, and many species show aggression outside of the breeding season, when the gonads are regressed and circulating levels of gonadal steroids are relatively low. Studies in diverse avian and mammalian species suggest that adrenal dehydroepiandrosterone (DHEA), an androgen precursor and prohormone, is important for the expression of aggression when gonadal T synthesis is low. Circulating DHEA can be converted into active sex steroids within the brain. In addition, the brain can synthesize sex steroids de novo from cholesterol, thereby uncoupling brain steroid levels from circulating steroid levels. These alternative mechanisms to provide sex steroids to specific neural circuits may have evolved to avoid the costs of high circulating T levels during the non-breeding season. Physiological indicators of season (e.g., melatonin) may allow animals to switch from one neuroendocrine mechanism to another across the year. DHEA and neurosteroids are likely to be important for the control of multiple behaviors in many species, including humans. These studies yield fundamental insights into the regulation of DHEA secretion, the mechanisms by which DHEA affects behavior, and the brain regions and neural processes that are modulated by DHEA. It is clear that the brain is an important site of DHEA synthesis and action.This article is part of a Special Issue entitled ‘Essential role of DHEA’.