Estrogen Receptor (ER) β Modulates ERα Responses to Estrogens in the Developing Rat Ventromedial Nucleus of the Hypothalamus

The mechanisms by which estradiol exerts specific actions on neural function are unclear. In brain the actions of estrogen receptor (ER) α are well documented, whereas the functions of ERβ are not yet fully elucidated. Here, we report that ERβ inhibits the activity of ERα in an anatomically specific manner within the neonatal (postnatal d 7) brain. Using selective agonists we demonstrate that the selective activation of ERα in the relative absence of ERβ activation induces progesterone receptor expression to a greater extent than estradiol alone in the ventromedial nucleus, but not the medial preoptic nucleus, despite high ERα expression. Selective activation of ERβ attenuates the ERα-mediated increase in progesterone receptor expression in the ventromedial nucleus but has no effect in medial preoptic nucleus. These results suggest that ERα/ERβ interactions may regulate the effects of estrogens on neural development and reveal the neonatal brain as a unique model in which to study the specificity of steroid-induced gene expression.