Steroid metabolising enzymes in the determination of brain gender

The neurotrophic effects of oestrogen formed in the brain are important in brain sexual differentiation of the central nervous system and behaviour. A romatase, converting testosterone to oestradiol-17 beta, is a key enzyme in volved in brain development. In primary cell cultures of foetal hypothalamu s, we have found that male neurones consistently have higher aromatase acti vity than in the female. Using a specific antibody to the mouse aromatase, immunoreactivity was localized in the neural soma and neurites in hypothala mic cultures. Additionally more male foetal hypothalamus neurones express a romatase than in the female. Testosterone increases aromatase activity in p arallel with a greater number of aromatase-immunoreactive neurones. Testost erone also increases soma size, neurite length, and branching of cultured h ypothalamic neurones. The neuronal aromatase activity appears to be sensiti ve to the inductive effects of androgen only during the later stages of foe tal development. Endogenous inhibitors of the aromatase are also likely to have a regulatory role. This work suggests that regulation of a network of aromatase neurones, sensitive to the hormonal environment of the hypothalam us, may determine when oestrogens are available for neurotrophic effects un derlying brain differentiation. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.