Phytoestrogen action in the adult and developing brain

Abstract Soy isoflavonoids are plant phytoestrogens available as dietary supplements and are increasingly advocated as a natural alternative to oestrogen replacement therapy. As weak oestrogen agonists/antagonists with a range of other enzymatic activities, the isoflavonoids provide a useful model to investigate the actions of endocrine disruptors. Here, the activational and organisational effects of these compounds on the brain are reviewed. In spite of their preferential affinity for oestrogen receptor (ER)beta in vitro, isoflavonoids act in vivo through both ERalpha and ERbeta. Their neurobehavioural actions are largely anti-oestrogenic, either antagonising or producing an action in opposition to that of oestradiol. Small, physiologically relevant exposure levels can alter oestrogen-dependent gene expression in the brain and affect complex behaviour in a wide range of species. The implications for these findings in humans, and particularly in infants, largely remain uninvestigated but are a subject of increasing public interest.