Preautonomic neurons in the paraventricular nucleus of the hypothalamus contain estrogen receptor β

Central actions of estrogen (E2) include, among others, modulation of autonomic and cardiovascular function. Despite the well-known influence of sex steroid hormones on the incidence of cardiovascular disorders, little is known about the neural substrates and receptors mediating central E2 actions on autonomic function. The paraventricular nucleus of the hypothalamus (PVN) is an important site for the integration of neuroendocrine and autonomic function. Interestingly, while this region was originally found to lack the classical ERα receptor, recent studies demonstrated a high degree of expression of the ERβ subtype. To determine specifically whether autonomic-related neurons in the PVN express ERβ, thus constituting a neuronal substrate for central E2 actions on autonomic function, we carried out an immunohistochemical study of ERβ expression in a subpopulation of PVN neurons that innervate the rostroventrolateral medulla (RVLM). ERβ immunostained neurons were found in medial and caudal aspects of the PVN, overlapping with the distribution of RVLM-projecting neurons. Overall, ∼50% of RVLM-projecting PVN neurons expressed ERβ immunoreactivity. Interestingly, the degree of colocalization was found to be sex-dependent (higher expression in males), and varied according to the topographical distribution of neurons within the PVN. ERβ immunoreactivity was also observed in magnocellular compartments of the PVN, although this appeared to be consistently weaker than that observed in autonomic-related subnuclei. These studies demonstrate for the first time ERβ expression in identified autonomic-related neurons in the PVN, and suggest that these neurons constitute an important neuronal substrate mediating E2 actions on autonomic and cardiovascular control.