Genistein Affects ERβ- But Not ERα-Dependent Gene Expression in the Hypothalamus.

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 ER and ER -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 ER and ER -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 ER and ER in the hypothalamus. Genistein had no effect, in either the presence or absence of 17 -E2, on oxytocin receptor density in the ventromedial nucleus of the hypothalamus, an estrogendependent action thought to be regulated via ER . However, genistein increased ER mRNA expression in the paraventricular nucleus of the hypothalamus by 24%, whereas 17 -E2 decreased ER mRNA expression by 26%, a process likely mediated by ER itself. These results suggest that at this dose, genistein has antiestrogenic action through ER in the paraventriculr nucleus but negligible activity through ER in the brain. (Endocrinology 143: 2189–2197, 2002)