A REVIEW OF BRAIN AROMATASE CYTOCHROME-P450

Aromatase cytochrome P450 (P450(AROM)) enzyme activity catalyzes the c onversion of androgens to estrogens in specific brains areas. During c entral nervous system development local estrogen formation influences the sexual differentiation of neural structures (i.e., by increasing n eurite growth and establishing neural circuitry) and modulates neuroen docrine/reproductive functions and sexual behavior. More than 20 years ago, in 1970, Naftolin et al. provided preliminary direct evidence fo r the aromatization of androgens by central neuroendocrine tissues. Th is work created the foundation for the brain aromatase hypothesis. A r eview of past and recent data reveals the importance of brain aromatas e in the development and function of the central nervous system. This review re-examines the aromatase hypothesis in light of recent data an d a theoretical proposal is presented in reference to the aromatase me chanism. The metabolic pathway of androgen metabolism by the aromatase cytochrome P450 pathway, cell type, distribution, developmental profi le, and regulation of brain aromatase is also presented. The complex n ature of brain aromatase is exemplified by recent molecular biology st udies examining the expression of aromatase cytochrome P450 during pre natal/postnatal development. Data derived from these studies provide i nsight into the regulation of the brain aromatase cytochrome P450 gene and suggest an additional level of control for the expression of brai n aromatase. These findings present evidence for the utilization of al ternative promoter(s) in man and rodents in driving aromatase gene exp ression in brain. It is clear that molecular mechanism(s) account for the diverse expression of aromatase in different neural tissue sites a nd during various physiological states or developmental periods. There fore, further study is necessary in order to understand the significan ce of the regulation of local estrogen biosynthesis by the aromatase c ytochrome P450 gene during prenatal and postnatal development due to t he dramatic impact these estrogen molecules have on neural development and their influence on reproductive function and behavior.