Estrogen receptor β expression in the mouse forebrain: age and sex differences

Estrogen receptors regulate multiple brain functions, including stress, sexual, and memory-associated behaviors as well as controlling neuroendocrine and autonomic function. During development, estrogen signaling is involved in programming adult sex differences in physiology and behavior. Expression of estrogen receptor α changes across development in a region-specific fashion. By contrast, estrogen receptor β (ERβ) is expressed in many brain regions, yet few studies have explored sex and developmental differences in its expression, largely because of the absence of selective reagents for anatomical localization of the protein. This study utilized bacterial artificial chromosome transgenic mice expressing ERβ identified by enhanced green fluorescent protein (EGFP) to compare expression levels and distribution of ERβ in the male and female mouse forebrain on the day of birth (P0), on postnatal day 4 (P4), and on P21. By using qualitative analysis, we mapped the distribution of ERβ-EGFP and found developmental alterations in ERβ expression within the cortex, hippocampus, and hypothalamic regions including the arcuate, ventromedial, and paraventricular nuclei. We also report a sex difference in ERβ in the bed nucleus of the stria terminalis, with males showing greater expression at P4 and P21. Another sex difference was found in the anteroventral periventricular nucleus of P21, but not P0 or P4, mice, in which ERβ-EGFP-immunoreactive cells were densely clustered near the third ventricle in females but not males. These developmental changes and sex differences in ERβ indicate a mechanism through which estrogens might differentially affect brain functions or program adult physiology at select times during development.