Genistein affects ERβ- but not ERα-dependent gene expression in the hypothalamus

Abstract

Isoflavone phytoestrogens are growing increasingly popular because of their reported cardiovascular and anticarcinogenic properties, but the effects of these compounds in the brain are largely unknown. In a previous study, we found that an isoflavone supplement, containing a mixture of soy phytoestrogens, inhibited estrogen-dependent female sexual behavior and was antiestrogenic for both ERα- and ERβ-dependent gene expression in the hypothalamus. Here we examined the impact of the soy isoflavone genistein, a major component of the supplement, on estrogen-dependent female sexual behavior and ERα- and ERβ-dependent gene expression in the rat brain. Genistein, at a dietary concentration of 100 or 500 ppm had no effect on lordosis behavior in rats. However, at 500 ppm genistein had differential activity through ERα and ERβ in the hypothalamus. Genistein had no effect, in either the presence or absence of 17β-E2, on oxytocin receptor density in the ventromedial nucleus of the hypothalamus, an estrogen-dependent action thought to be regulated via ERα. However, genistein increased ERβ mRNA expression in the paraventricular nucleus of the hypothalamus by 24%, whereas 17β-E2 decreased ERβ mRNA expression by 26%, a process likely mediated by ERβ itself. These results suggest that at this dose, genistein has antiestrogenic action through ERβ in the paraventricular nucleus but negligible activity through ERα in the brain.