New roles for estrogen receptor β in behavior and neuroendocrinology

In this review we critically examine the data on functions of the estrogen receptor beta (ER beta) in both behavior and neuroendocrinology. The influence of estradiol via the ER beta has been assessed using several methods: estrogen receptor knockout mice, specific ER beta selective agonists, and phytoestrogens which preferentially bind to ER beta rather than ER alpha. The behavior for which a solid database and consensus is forming is anxiety; activation of ER beta reduces anxiety on a number of tasks and in several species. Moreover, the relationship between ER beta and serotonin may be critical for the regulation of this behavior by estradiol. There have been very few studies on learning and memory but the little we know suggests that ER beta is involved in visuospatial learning; in its absence learning is inhibited. Recent work has suggested a unique function for ER beta in sexual differentiation; its activation in male neonates may promote deferninization of sexual behavior. Several neurotransmitter-containing neurons in the rat paraventricular nucleus coexpress ER beta including; vasopressin, oxytocin, prolactin, and to a lesser extent corticotrophin releasing hormone. Given the potential for ER beta to interact with these important neurotransmitters and its co-expression in gonadotropin releasing hormone neurons it is surprising how normal the hypothalamic-pituitary-adrenal and -gonadal axes appear to be in ER beta knockout mice. Either this represents a species difference (the neuroanatomy has been conducted in the rat) or compensatory actions of ER alpha or other mechanisms. Exciting avenues for future research include; in vivo interactions between ER alpha and ER beta, actions of non-estrogenic ligands with ER-beta, and the role of ER beta in sexual differentiation. (c) 2006 Elsevier Inc. All rights reserved.