Developmental Profile and Regulation of Brain Estrogen Synthesis by Aromatase

• Aromatase cytochrome P450 enzyme catalyzes the formation ofestrogenfrom androgen in distinct regions of the vertebrate brain. During neural development, local estrogen synthesis is required for the sexual differentiation of male brain characteristics and the differentiation of neural circuits Involved in sex-specific behaviors and neuro endocrine functions. A common phenomenon in all species studied so far is that the male brain displays much higher and. brain region-specific aromatase expression during distinct periods of brain development than the female one. An important question arising from these findings is which factor(s) play a role in regulating estrogen formation in a sexand brain region-specific fashion. Among the factors investigated, androgens have been found to be the most powerful regulators of brain aromatase. In vitro experiments using primary cell cultures of embryonic mouse brains showed that sex differences in aromatase activity in hypothalamic cells develop, at first, independently of gonadal steroids. Later during embryonic development, aromatase expression is regulated in a regionand sex-specific way by circulating androgens. Hypothalamic aromatase neurons are inost sensitive to androgen exposure whereas cortical and midbnlin,(> H'x are insensitive. Moreover, androgens affect morpliolt\\!*col. maturation ofaromatase-immunoreactive cells by