DHEA in Prenatal and Postnatal Life: Implications for Brain and Behavior

Dehydroepiandrosterone (DHEA) and its sulfated congener (DHEAS) are the principal C₁₉ steroid produced by the adrenal gland in many mammals, including humans. It is secreted in high concentrations during fetal life, but synthesis decreases after birth until, in humans and some other primates, there is a prepubertal surge of DHEA production by the adrenal gland-a phenomenon known as adrenarche. There remains considerable uncertainty about the physiological role of DHEA and DHEAS. Moreover, the origin of the trophic drives that determine the waxing and waning of DHEA synthesis are poorly understood. These gaps in knowledge arise in some measure from the difficulty of understanding mechanistic determinants from observations made opportunistically in humans and primates, and have stimulated a search for other suitable species that exhibit adrenarche- and adrenopause-like changes of adrenal function. DHEA and DHEAS are clearly neuroactive steroids with actions at several neurotransmitter receptors; indeed, DHEA is now known to be also synthesized by many parts of the brain, and this capacity undergoes ontogenic changes, but whether this is dependent or independent of the changes in adrenal synthesis is unknown. In this chapter we review key contributions to this field over the last 50+ years, and speculate on the importance of DHEA for the brain, both during development and for maturation and aging of cerebral function and behavior.