Sexual differentiation of the bed nucleus of the stria terminalis in humans may extend into adulthood

Gonadal steroids have remarkable developmental effects on sex-dependent brain organization and behavior in animals. Presumably, fetal or neonatal gonadal steroids are also responsible for sexual differentiation of the human brain. A limbic structure of special interest in this regard is the sexually dimorphic central subdivision of the bed nucleus of the stria terminalis (BSTc), because its size has been related to the gender identity disorder transsexuality. To determine at what age the BSTc becomes sexually dimorphic, the BSTc volume in males and females was studied from midgestation into adulthood. Using vasoactive intestinal polypeptide and somatostatin immunocytochemical staining as markers, we found that the BSTc was larger and contains more neurons in men than in women. However, this difference became significant only in adulthood, showing that sexual differentiation of the human brain may extend into the adulthood. The unexpectedly late sexual differentiation of the BSTc is discussed in relation to sex differences in developmental, adolescent, and adult gonadal steroid levels.