Age-Related Changes in Estrogen Receptor β in Rat Hypothalamus: A Quantitative Analysis

Abstract

Although the estrogen receptor beta (ER beta) 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 ER beta 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 ER beta-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 ER beta and the obligatory N-methyl-D-aspartate receptor subunit, NR1. We observed a significant age-related decrease in ER beta cell number in the AVPV, but not the pBST. No significant effect of estrogen on ER beta cell number was detected in either brain region at any age. Approximately 10% and 3% of cells expressing ER beta 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 ER beta cell number that are region specific; 2) this expression is not altered by estrogen replacement; and 3) a subset of ER beta-positive cells coexpresses NR1.

Age-related changes in the expression of ER-β mRNA in the female rat brain

“…The age-related decreases in the level of ER-β protein have reported in the cortex of the intact and ovariectomized female mice and in the hippocampus of female rats (Mehra et al, 2005), which is in agreement with our and previous data for ER-β mRNA. Chakraborty et al (2003b) reported that ER-β immunoreactive cells decreased with age in the anteroventral periventricular nucleus but not the bed nucleus of the stria terminalis. By contrast, we found no changes in ER-β mRNA levels in either brain region.…”

Postpubertal decrease in hippocampal dendritic spines of female rats

“…For the stereologic analysis, the coefficients of variation (CV = standard deviation/mean) and coefficient of error (CE) of the stereologic estimates were calculated as previously described (Tang et al, 2004;Chakraborty et al, 2003aChakraborty et al, , 2003b. For each animal, CE's ranged from 0.05 to 0.12, and mean CE's were 0.07 to 0.09 per group.…”

“…All quantitative analyses were performed using a computer-assisted morphometry system consisting of a Zeiss Axioplan 2 photomicroscope equipped with an Applied Scientific Instrumentation MS-2000 XYZ computer-controlled motorized stage, a DAGE-MTI DC-330 video camera, a Gateway microcomputer, and the Stereo Investigator morphometry and stereology software (MicroBrightField version 5, Wiliston, VT). All these procedures have been described previously and are routine within the laboratories (Hao et al, 2003;Tang et al, 2004;Chakraborty et al, 2003aChakraborty et al, , 2003b. The contours of CA1sr were traced at 2.5× magnification.…”

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

“…The AVPV is a small preoptic brain region that is abundant in nuclear hormone receptors such as ERα [25], ERβ [108,26], AR [143], and PR [122] in a sexually dimorphic manner (ERα [27], ERβ [108], PR [122]). The AVPV of rats is larger in female than male rodents [18,43,150], due to influences of both estradiol and testosterone during the early postnatal (and possibly prenatal) periods [43,150,142].…”