SEXUAL DIMORPHISM IN THE DEVELOPMENTAL REGULATION OF BRAIN AROMATASE

Steroid sex hormones have an organizational role in gender-specific br ain development. Aromatase (cytochrome P450(AR)), converting testoster one (T) to estradiol-17 beta (E(2)) is a key enzyme in brain developme nt and the regulation of aromatase determines the availability of E(2) effective for neural differentiation. Gender differences in brain dev elopment and behaviour are likely to be influenced by E(2) acting duri ng sensitive periods. This differentiating action has been demonstrate d in rodent and avian species, but also probably occurs in primates in cluding humans. In rodents, E(2) is formed in various hypothalamic are as of the brain during fetal and postnatal development. The question c onsidered here is whether hypothalamic aromatase activity is gender-sp ecific during sensitive phases of behavioural and brain development, a nd when these sensitive phases occur. In vitro preoptic and limbic aro matase activity has been measured in two strains of wild mice, genetic ally selected for behavioural aggression based on attack latency, and in the BALB/c mouse. Short attack latency males show a different devel opmental pattern of aromatase activity in hypothalamus and amygdala to long attack latency males. Using primary brain cell cultures of the B ALB/c mouse, sex differences in hypothalamic aromatase activity during both early embryonic and later perinatal development can be demonstra ted, with higher E(2) formation in males. The sex dimorphisms are brai n region specific, since no differences between male and female are de tectable in cultured cortical cells. Immunoreactive staining with a po lyclonal aromatase antibody identifies a neuronal rather than an astro glial localization of the enzyme. T increases fetal brain aromatase ac tivity and numbers of aromatase-immunoreactive hypothalamic neuronal c ell bodies. T appears to influence the growth of hypothalamic neurons containing aromatase. Differentiation of sexually dimorphic brain mech anisms may involve maturation of a gender-specific network of estrogen -forming neurons which are steroid-sensitive in early development.