New roles for estrogen receptor β in behavior and neuroendocrinology

In this review we critically examine the data on functions of the estrogen receptor β (ERβ) in both behavior and neuroendocrinology. The influence of estradiol via the ERβ has been assessed using several methods: estrogen receptor knockout mice, specific ERβ selective agonists, and phytoestrogens which preferentially bind to ERβ rather than ERα. The behavior for which a solid database and consensus is forming is anxiety; activation of ERβ reduces anxiety on a number of tasks and in several species. Moreover, the relationship between ERβ 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 ERβ is involved in visuospatial learning; in its absence learning is inhibited. Recent work has suggested a unique function for ERβ in sexual differentiation; its activation in male neonates may promote defeminization of sexual behavior. Several neurotransmitter-containing neurons in the rat paraventricular nucleus coexpress ERβ including; vasopressin, oxytocin, prolactin, and to a lesser extent corticotrophin releasing hormone. Given the potential for ERβ 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 ERβ knockout mice. Either this represents a species difference (the neuroanatomy has been conducted in the rat) or compensatory actions of ERα or other mechanisms. Exciting avenues for future research include; in vivo interactions between ERα and ERβ, actions of non-estrogenic ligands with ERβ, and the role of ERβ in sexual differentiation.