Age-related changes in estrogen receptor β in rat hypothalamus: A quantitative analysis

Abstract

Although the estrogen receptor β (ERβ) is a major target for actions of estrogen on the brain, little is known about its neural expression during aging, when levels and the mode of estrogen release undergo substantial changes. Therefore, in the present study we examined effects of aging and estrogen treatment on the number of cells expressing the ERβ in female rats. Two regions relevant to reproductive function were analyzed: the anteroventral periventricular nucleus (AVPV) and the principal nucleus of the bed nucleus of the stria terminalis (pBST). The numbers of ERβ-expressing cells were quantified using an unbiased stereological approach. Female rats were used at three ages [young (3-4 months), middle-aged (10-12 months), and old (24-26 months)], with or without estrogen replacement. Because the estrogen milieu impacts the function of neurotransmitter receptors such as the N-methyl-D-aspartate receptor in the brain, we also investigated the colocalization of ERβ and the obligatory N-methyl-D-aspartate receptor subunit, NR1. We observed a significant age-related decrease in ERβ cell number in the AVPV, but not the pBST. No significant effect of estrogen on ERβ cell number was detected in either brain region at any age. Approximately 10% and 3% of cells expressing ERβ also coexpressed NR1 in AVPV and pBST, respectively, and this did not differ with age or treatment. Taken together, our results demonstrate 1) there are age-related changes in ERβ cell number that are region specific; 2) this expression is not altered by estrogen replacement; and 3) a subset of ERβ-positive cells coexpresses NR1.